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Genetic Counseling (genetic + counseling)
Kinds of Genetic Counseling Selected AbstractsCurrent awareness in prenatal diagnosisPRENATAL DIAGNOSIS, Issue 9 2009Article first published online: 28 AUG 200 In order to keep subscribers up-to-date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of prenatal diagnosis. Each bibliography is divided into 21 sections: 1 Reviews; 2 General Interest; 3 Normal Fetal Development; 4 Preimplantation Genetic Diagnosis; 5 First Trimester Diagnosis; 6 Second Trimester Diagnosis; 7 Fetal Imaging: General; Ultrasound; MRI; 8 Maternal Serum Screening for Aneuploidy; 9 Screening for Carriers of Genetic Abnormality; 10 Molecular Cytogenetics: Metaphase Cytogenetics/FISH; Array CGH; 11 Fetal Cells in Maternal Circulation; 12 Fetal DNA/RNA in Maternal Body Fluids; 13 Fetal Therapy; 14 Psychosocial and Ethical Aspects; 15 Epidemiology and Environmental Factors; 16 Developmental and Placental Pathology; 17 Genetic Counseling. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted [source] Current awareness in prenatal diagnosisPRENATAL DIAGNOSIS, Issue 4 2009Article first published online: 30 MAR 200 In order to keep subscribers up-to-date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of prenatal diagnosis. Each bibliography is divided into 20 sections: 1 Reviews; 2 General Interest; 3 Normal Fetal Development; 4 Preimplantation Genetic Diagnosis; 5 First Trimester Diagnosis; 6 Second Trimester Diagnosis; 7 Fetal Imaging: General; Ultrasound; MRI; 8 Maternal Serum Screening for Aneuploidy; 9 Screening for Carriers of Genetic Abnormality; 10 Molecular Cytogenetics: Metaphase Cytogenetics/FISH; Array cGH; 11 Fetal Cells in Maternal Circulation; 12 Fetal DNA/RNA in Maternal Body Fluids; 13 Fetal Therapy; 14 Psychosocial and Ethical Aspects; 15 Epidemiology and Environmental Factors; 16 Developmental and Placental Pathology; 17 Genetic Counseling. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted [source] Current awareness in prenatal diagnosisPRENATAL DIAGNOSIS, Issue 3 2009Article first published online: 26 FEB 200 In order to keep subscribers up-to-date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of prenatal diagnosis. Each bibliography is divided into 20 sections: 1 Reviews; 2 General Interest; 3 Normal Fetal Development; 4 Preimplantation Genetic Diagnosis; 5 First Trimester Diagnosis; 6 Second Trimester Diagnosis; 7 Fetal Imaging: General; Ultrasound; MRI; 8 Maternal Serum Screening for Aneuploidy; 9 Screening for Carriers of Genetic Abnormality; 10 Molecular Cytogenetics: Metaphase Cytogenetics/FISH; Array cGH; 11 Fetal Cells in Maternal Circulation; 12 Fetal DNA/RNA in Maternal Body Fluids; 13 Fetal Therapy; 14 Psychosocial and Ethical Aspects; 15 Epidemiology and Environmental Factors; 16 Developmental and Placental Pathology; 17 Genetic Counseling. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted [source] Genetic Counseling and the Advanced Practice Oncology Nursing Role in a Hereditary Cancer Prevention Clinic: Hereditary Breast Cancer Focus (Part I)THE BREAST JOURNAL, Issue 2009Carrie L. Snyder MSN Abstract:, Interest in hereditary breast cancer has increased rapidly among all health care providers as well as the laity. A major problem for health care providers, however, is the time and skill required for gathering family history, interpreting the pedigree, and providing genetic counseling for the high-risk patient so that BRCA testing, when indicated, can be pursued and screening and prevention strategies employed by the patient. The fields of hereditary cancer and molecular biology have developed at a rate that makes it difficult for physicians to keep up with this explosive knowledge. Therefore, "Who is going to take care of all of these crucial matters for patient benefit?" is a germane question. Our experience has confirmed that the advanced practice oncology nurse who is interested in cancer genetics can become skilled at providing this service to the patient and his/her family. This study portrays the role of such an oncology nurse in meeting this important public health challenge, with special attention devoted to the logistics of this role in the rapidly emerging field of hereditary breast cancer. [source] A study of argumentation in a causal probabilistic humanistic domain: Genetic counselingINTERNATIONAL JOURNAL OF INTELLIGENT SYSTEMS, Issue 1 2007Nancy Green We present the results of an in-depth qualitative analysis of argumentation in two genetic counseling patient letters. In addition to argumentation techniques designed for medical experts, we found other types of causal argumentation designed for lay readers, reflecting the educational and supportive counseling functions of these letters. Analysis was facilitated by use of a coding scheme for representing causal probabilistic biomedical content of the letters as Bayesian networks. We define the argument techniques used in the letters in terms of Bayesian network, semantic network, argumentation theory, and user model concepts rather than in terms of genetics concepts. © 2007 Wiley Periodicals, Inc. Int J Int Syst 22: 71,93, 2007. [source] Genetic counseling of adults with Williams syndrome: A first study,AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 2 2010Katrina Farwig Abstract We report on a study of genetic counseling to 43 adults with Williams syndrome (WS). Participants were initially asked what they knew about how WS occurs. Genetic counseling was provided with a focus on the basic genetics of WS, recurrence risk, and on participants' attitudes toward socio-cultural topics. Forty-nine percent indicated that they would be okay or happy if their baby had WS, 44% said they would be sad or upset, and 5% were unsure. The sad/upset group was significantly older than the okay/happy group and a significantly higher proportion of the former group indicated that they did not plan to have children. During the post-counseling session participants were questioned to determine if they recalled the facts previously presented. Eighty-one percent correctly gave the odds that their child would have WS. Fifty-three percent considered the 50,50 odds to be a high chance. After genetic counseling, 61% were able to state something that had been taught and 88% indicated that they would want to test their baby for WS before birth. Ninety-eight percent would recommend genetic counseling to others. Findings indicate that based on the type of genetic counseling provided in this study, the majority of individuals with WS,a genetic disorder associated with intellectual disability but with relative strengths in (concrete) language and in verbal rote memory,are able to learn simple facts about the genetics of WS and are eager to respond to socio-cultural questions regarding topics typically included in genetic counseling sessions. © 2010 Wiley-Liss, Inc. [source] Genetic counseling and "molecular" prenatal diagnosis of holoprosencephaly (HPE),AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 1 2010Sandra Mercier Abstract Holoprosencephaly (HPE) is a structural anomaly of the developing brain in which the forebrain fails to divide into two separate hemispheres and ventricles. The poor prognosis in the most severe forms justifies the importance of genetic counseling in affected families. The genetic counseling requires a thorough clinical approach given the extreme variability of phenotype and etiology. The karyotype is an essential diagnostic tool. Since mutations in the four major genes (SHH, ZIC2, SIX3, and TGIF) have been identified in HPE patients, molecular study is performed routinely in nonsyndromic HPE. New molecular tools, such as array-CGH analysis, are now part of the diagnostic process. Prenatal diagnosis is based primarily on fetal imaging, but "molecular" prenatal diagnosis can be performed if a mutation has been previously identified in a proband. Interpretations of molecular diagnosis must be given with caution, given the lack of strict genotype,phenotype correlation, and should be offered in addition to fetal imaging, using ultrasound followed by fetal MRI. We report on our experience of 15 molecular prenatal diagnoses from chorionic villi or amniotic fluid sampling. In eight instances, we were able to reassure the parents after taking into account the absence of the mutation in the fetus, previously identified before in a parent and/or a proband. Fetal RMI was normal later in pregnancy, and no child had medical problems after birth. The mutation was found in the seven other cases: four children were born, either without brain malformation and asymptomatic, or had a less severe form than the index case. © 2010 Wiley-Liss, Inc. [source] The Genetic Counseling Video Project (GCVP): Models of practice,AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 4 2006D. Roter Abstract Genetic counseling is conceptualized as having both "teaching" and "counseling" functions; however, little is known about how these functions are articulated in routine practice. This study addresses the question by documenting, on videotape, the practices of a national sample of prenatal and cancer genetic counselors (GCs) providing routine pre-test counseling to simulated clients (SCs). One hundred and seventy-seven GCs recruited at two annual conferences of the National Society of Genetic Counselors (NSGC) were randomly assigned to counsel one of six female SCs of varying ethnicity, with or without a spouse, in their specialty. One hundred and fifty-two videotapes were coded with the Roter Interaction Analysis System (RIAS) and both GCs and SCs completed evaluative questionnaires. Two teaching and two counseling patterns of practice emerged from cluster analysis. The teaching patterns included: (1) clinical teaching (31%) characterized by low psychosocial, emotional and facilitative talk, high levels of clinical exchange, and high verbal dominance; and (2) psycho-educational teaching (27%) characterized by high levels of both clinical and psychosocial exchange, low levels of emotional and facilitative talk, and higher verbal dominance. The counseling patterns included: (1) supportive counseling (33%) characterized by low psychosocial and clinical exchange, high levels of emotional and facilitative talk, and low verbal dominance; and (2) psychosocial counseling (9%) with high emotional and facilitative talk, low clinical and high psychosocial exchange, and the lowest verbal dominance. SCs ratings of satisfaction with communication, the counselor's affective demeanor, and the counselor's use of non-verbal skills were highest for the counseling model sessions. Both the teaching and counseling models seem to be represented in routine practice and predict variation in client satisfaction, affective demeanor, and nonverbal effectiveness. © 2006 Wiley-Liss, Inc. [source] Acute hemorrhagic leukoencephalitis in male sibsAMERICAN JOURNAL OF MEDICAL GENETICS, Issue 4 2002D. Ross McLeod Abstract Male siblings developed acute hemorrhagic leukoencephalitis (AHL) at age five months and eight months, respectively. This rare condition has not been reported in individuals less than two years of age or with a recurrence in the family. The diagnosis was based on neuropathologic features after ruling out potentially mimicking conditions. Genetic counseling of early onset AHL should include the possibility of recurrence in siblings. © 2001 Wiley-Liss, Inc. [source] Penetrance estimation of TTR familial amyloid polyneuropathy (type I) in Brazilian familiesEUROPEAN JOURNAL OF NEUROLOGY, Issue 3 2009M. A. C. Saporta Background and purpose:, Familial amyloid polyneuropathy (FAP) type I is a severe autosomal dominant inherited neuropathy associated with mutations in the transthyretin (TTR) gene. Significant phenotypic variability is seen amongst families with distinct geographic origin, especially regarding penetrance and age of onset. The aim of this study was to estimate the penetrance of FAP in Brazilian families. Methods:, Twenty-two distinct families were ascertained through genetically confirmed index cases and included in this study. Genealogical and clinical data were obtained from a total of 623 individuals, including 126 affected by FAP. In 15 families, TTR genotyping was performed in all available relatives (n = 86), after informed written consent. Seven families did not consent for genetic testing, but agreed to provide clinical and genealogical data. Penetrance was estimated using a previously described method based on survival analysis and corrected for ascertainment bias. Results:, Mean age of onset in our sample was 34.5 years, with a significant earlier onset in males (31.1 vs. 35.9, P < 0.0001). The penetrance of FAP in our sample was estimated as 83% (95% CI: 66,99) after 60 years. Conclusion:, Our results provide new information on FAP in Brazilian patients and may be helpful in the genetic counseling of this population. [source] Juvenile-onset neuronal ceroid lipofuscinosis with infantile CLN1 mutation and palmitoyl-protein thioesterase deficiencyEUROPEAN JOURNAL OF NEUROLOGY, Issue 4 2007R. Kälviäinen Accurate diagnosis, especially in progressive hereditary diseases, is essential for the treatment and genetic counseling of the patient and the family. Neuronal ceroid lipofuscinoses (NCL) are amongst the most common groups of neurodegenerative diseases. Infantile, juvenile, and adult-onset types with multiple genotype,phenotype associations have been described. A fluorimetric enzyme assay for palmitoyl protein thioesterase (PPT) from leukocytes and fibroblasts has been previously developed to confirm the diagnosis of infantile NCL. We describe a patient with juvenile-onset NCL phenotype with a new CLN1 mutation and deficient PPT activity. Over 40 different mutations have been found in patients with PPT deficiency, indicating that screening for known mutations is not an efficient way to diagnose this disorder. Therefore, PPT enzyme analysis should precede mutation analysis in suspected PPT deficiency, particularly in patients with granular osmiophilic deposits (GROD) or in patients who have negative ultrastructural data. The use of enzyme assay led to the diagnosis of this patient with juvenile-onset Finnish variant NCL with PPT deficiency, and we expect that greater awareness of the utility of the enzymatic assay may lead to identification of other similar cases awaiting a definitive diagnosis. [source] Paternal germline mosaicism in Herlitz junctional epidermolysis bullosaEXPERIMENTAL DERMATOLOGY, Issue 5 2002Peter B. Cserhalmi-Friedman Abstract: We studied a single patient with the lethal (Herlitz) type of junctional epidermolysis bullosa (H-JEB). Screening for mutations in the LAMB3 gene in the patient revealed the previously described hotspot mutation R635X and a novel one basepair deletion in exon 10. The single basepair deletion 1094delA could be detected in the clinically unaffected mother, while the nonsense mutation R635X could not be found in the peripheral blood DNA of either parent. After excluding non-paternity by microsatellite analysis using random markers on chromosomes 3, 8 and 18, we determined that the mutation R635X in the proband was most likely the result of a de novo event or alternatively, germline mosaicism. The parents requested prenatal diagnosis for a second pregnancy, and while the maternal mutation 1094delA could not be detected in DNA from the fetus, unexpectedly, the mutation R635X was present in the chorionic villus DNA. These findings were most consistent with paternal germline mosaicism for the recessive mutation R635X. The results have had a significant impact on the genetic counseling in this family. To our knowledge, this study represents the first documented case of germline mosaicism in junctional epidermolysis bullosa, and serves as a reminder that germline mosaicism should be considered in cases in which a ,new' mutation is found in the offspring of a clinically and/or genetically unaffected parent. [source] Huntington's disease with onset ages greater than 60 yearsGERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 1 2007Kunihiro Yoshida We examined five patients with late-onset Huntington's disease (HD), who developed chorea as an initial symptom at age 60 or later. The mean disease duration from the onset of chorea was approximately 8 years (range, 2,16 years). All carried expanded HD alleles with 39 or 40 CAG repeats. Cognitive or psychiatric decline was observed in four patients, the mean duration of the disease being approximately 10 years. One of them had been institutionalized in a nursing home undiagnosed for a long time. Late-onset HD patients with shorter repeat expansions may be overlooked in Japan. Non-disabling chorea, mild cognitive or psychiatric decline in such patients are sometimes unrecognized or misunderstood as aging-related phenomena, and do not come to medical attention. Considering the potential genetic risk to younger generations, however, genetic testing on such late-onset HD patients should be conducted with careful genetic counseling and psychological support for their family members. [source] MUTYH mutations associated with familial adenomatous polyposis: functional characterization by a mammalian cell-based assay,HUMAN MUTATION, Issue 2 2010Sara Molatore Abstract MUTYH -associated polyposis (MAP) is a colorectal cancer syndrome, due to biallelic mutations of MUTYH. This Base Excision Repair gene encodes for a DNA glycosylase that specifically mitigates the high mutagenic potential of the 8-hydroxyguanine (8-oxodG) along the DNA. Aim of this study was to characterize the biological effects, in a mammalian cell background, of human MUTYH mutations identified in MAP patients (137insIW [c.411_416dupATGGAT; p.137insIleTrp]; R171W [c.511C>T; p.Arg171Trp]; E466del [c.1395_1397delGGA; p.Glu466del]; Y165C [c.494A>G; p.Tyr165Cys]; and G382D [c.1145G>A; p.Gly382Asp]). We set up a novel assay in which the human proteins were expressed in Mutyh,/, mouse defective cells. Several parameters, including accumulation of 8-oxodG in the genome and hypersensitivity to oxidative stress, were then used to evaluate the consequences of MUTYH expression. Human proteins were also obtained from Escherichia coli and their glycosylase activity was tested in vitro. The cell-based analysis demonstrated that all MUTYH variants we investigated were dysfunctional in Base Excision Repair. In vitro data complemented the in vivo observations, with the exception of the G382D mutant, which showed a glycosylase activity very similar to the wild-type protein. Our cell-based assay can provide useful information on the significance of MUTYH variants, improving molecular diagnosis and genetic counseling in families with mutations of uncertain pathogenicity. Hum Mutat 30:1,8, 2009. © 2009 Wiley-Liss, Inc. [source] Myocilin allele-specific glaucoma phenotype database,HUMAN MUTATION, Issue 2 2008Alex W. Hewitt Abstract Glaucoma, a complex heterogenous disease, is the leading cause for optic nerve,related blindness worldwide. Since 1997, when mutations in the myocilin (MYOC) gene were identified as causing juvenile onset as well as a proportion of primary open-angle glaucoma (POAG), more than 180 variants have been documented. Approximately one in 30 unselected patients with POAG have a disease-causing myocilin mutation and it has been shown that firm genotype,phenotype correlations exist. We have compiled an online catalog of myocilin variants and their associated phenotypes. This locus-specific resource, to which future submissions can be made, is available online (www.myocilin.com; last accessed 28 August 2007). The database, constructed using MySQL, contains three related sheets that contain data pertaining to the information source, variant identified, and relevant study data, respectively. The website contains a list of all identified variants and summary statistics as well as background genomic information, such as the annotated sequence and cross-protein/species homology. Phenotypic data such as the mean±standard deviation (SD) age at POAG diagnosis, mean±SD maximum recorded intraocular pressure, proportion of patients requiring surgical intervention, and age-related penetrance can be viewed by selecting a particular mutation. Approximately 40% of the identified sequence variants have been characterized as disease causing, with the majority (,85%) of these being missense mutations. Preliminary data generated from this online resource highlight the strong genotype,phenotype correlations associated with specific myocilin mutations. The large-scale assimilation of relevant data allows for accurate comprehensive genetic counseling and the translation of genomic information into the clinic. Hum Mutat 29(2), 207,211, 2008. © 2007 Wiley-Liss, Inc. [source] Genotype,phenotype correlations in hereditary familial retinoblastoma,HUMAN MUTATION, Issue 3 2007Melissa Taylor Abstract We studied 50 unrelated pedigrees with a family history of retinoblastoma (Rb) (165 carriers of a RB1 mutation) to delineate the spectrum of RB1 germline mutations in familial Rb and to identify genotype,phenotype correlations as well as putative modifiers. Patients were followed at Institut Curie and they were examined by an ophthalmologist, a pediatrician, and a geneticist. All cases of familial Rb were determined via genetic counseling. Clinical features included disease status, laterality, age at diagnosis, mutation type, follow-up, and disease,eye ratio (DER). To eliminate mosaic cases, first-generation carriers displaying low-penetrance (LP) Rb were excluded from the analysis. Complete penetrance was the rule for nonsense and frameshift mutations (25 families) and high penetrance was observed for large rearrangements (eight families). Promoter (two families) and missense (two families) mutations displayed heterogeneous phenotypes and LP. Variable penetrance was observed for splice abnormalities (13 families) and was explained by in/out of frame mutations or respect of functional domains. Surprisingly, two families with the LP g.45867G>T/IVS6+1G>T mutation presented data that conflicted with the data reported in previous publications, as unaffected carriers had paternally inherited mutant alleles. Moreover, RNA analyses suggested that the lack of penetrance in unaffected carriers could be explained by an increase in expression levels of the wild-type allele. This observation prompted us to define a new class "3" of LP alleles. We believe this is the first large-scale study of familial Rb with a high level of homogeneity in the clinical and genetic analysis of patients and their relatives, thereby allowing for reliable intrafamilial genotype,phenotype correlations. Our analysis suggests in some cases the influence of modifier factors probably involved in mRNA level regulation and/or pRB pathway regulation. Hum Mutat 28(3), 284,293, 2007. © 2006 Wiley-Liss, Inc. [source] Comprehensive survey of mutations in RP2 and RPGR in patients affected with distinct retinal dystrophies: genotype,phenotype correlations and impact on genetic counseling,,HUMAN MUTATION, Issue 1 2007Valérie Pelletier Abstract X-linked forms of retinitis pigmentosa (RP) (XLRP) account for 10 to 20% of families with RP and are mainly accounted for by mutations in the RP2 or RP GTPase regulator (RPGR) genes. We report the screening of these genes in a cohort of 127 French family comprising: 1) 93 familial cases of RP suggesting X-linked inheritance, including 48 out of 93 families with expression in females but no male to male transmission; 2) seven male sibships of RP; 3) 25 sporadic male cases of RP; and 4) two cone dystrophies (COD). A total of 5 out of the 93 RP families excluded linkage to the RP2 and RP3 loci and were removed form the cohort. A total of 14 RP2 mutations, 12 of which are novel, were identified in 14 out of 88 familial cases of RP and 1 out of 25 sporadic male case (4%). In 13 out of 14 of the familial cases, no expression of the disease was noted in females, while in 1 out of 14 families one woman developed RP in the third decade. A total of 42 RPGR mutations, 26 of which were novel, were identified in 80 families, including: 69 out of 88 familial cases (78.4%); 2 out of 7 male sibship (28.6%); 8 out of 25 sporadic male cases (32.0%); and 1 out of 2 COD. No expression of the disease was noted in females in 41 out of 69 familial cases (59.4%), while at least one severely affected woman was recognized in 28 out of 69 families (40.6%). The frequency of RP2 and RPGR mutations in familial cases of RP suggestive of X-linked transmission are in accordance to that reported elsewhere (RP2: 15.9% vs. 6,20%; RPGR: 78.4% vs. 55,90%). Interestingly, about 30% of male sporadic cases and 30% of male sibships of RP carried RP2 or RPGR mutations, confirming the pertinence of the genetic screening of XLRP genes in male patients affected with RP commencing in the first decade and leading to profound visual impairment before the age of 30 years. Hum Mutat 28(1), 81,91, 2007. © 2006 Wiley-Liss, Inc. [source] Molecular diagnosis of inherited disorders: lessons from hemoglobinopathies,HUMAN MUTATION, Issue 5 2005George P. Patrinos Abstract Hemoglobinopathies constitute a major health problem worldwide, with a high carrier frequency, particularly in certain regions where malaria has been endemic. These disorders are characterized by a vast clinical and hematological phenotypic heterogeneity. Over 1,200 different genetic alterations that affect the DNA sequence of the human ,-like (HBZ, HBA2, HBA1, and HBQ1) and ,-like (HBE1, HBG2, HBG1, HBD, and HBB) globin genes are mainly responsible for the observed clinical heterogeneity. These mutations, together with detailed information about the resulting phenotype, are documented in the globin locus-specific HbVar database. Family studies and comprehensive hematological analyses provide useful insights for accurately diagnosing thalassemia at the DNA level. For this purpose, numerous techniques can provide accurate, rapid, and cost-effective identification of the underlying genetic defect in affected individuals. The aim of this article is to review the diverse methodological and technical platforms available for the molecular diagnosis of inherited disorders, using thalassemia and hemoglobinopathies as a model. This article also attempts to shed light on issues closely related to thalassemia diagnostics, such as prenatal and preimplantation genetic diagnoses and genetic counseling, for better-quality disease management. Hum Mutat 26(5), 399,412, 2005. © 2005 Wiley-Liss, Inc. [source] Screening of 25 Italian patients with Niemann-Pick a reveals fourteen new mutations, one common and thirteen private, in SMPD1,,HUMAN MUTATION, Issue 1 2004V. Ricci Abstract Niemann-Pick disease (NPD) results from the deficiency of lysosomal acid sphingomyelinase (SMPD1). To date, out of more than 70-disease associated alleles only a few of them have a significant frequency in various ethnic groups. In contrast, the remainder of the mutations are rare or private. In this paper we report the molecular characterization of an Italian series consisting of twenty-five NPD patients with the severe neurodegenerative A phenotype. Mutation detection identified a total of nineteen different mutations, including 14 novel mutations and five previously reported lesions. The known p.P189fs and the novel p.T542fs were the most frequent mutations accounting for 34% and 18% of the alleles, respectively. Screening the alleles for the three common polymorphisms revealed the variant c.1516G>A (exon 6) and the repeat in exon 1, but not the variant c.965C>T (exon 2). In absence of frequent mutations, the prognostic value of genotyping is limited. However, new genotype/phenotype correlations were observed for this disorder that could in the future facilitate genetic counseling and guide selection of patients for therapy. © 2004 Wiley-Liss, Inc. [source] A specific GFP expression assay, penetrance estimate, and histological assessment for a putative splice site mutation in BRCA1,HUMAN MUTATION, Issue 1 2003M.C. Southey Abstract Genetic testing for cancer predisposing mutations in BRCA1 and BRCA2 has been of benefit to many individuals from breast and ovarian cancer-prone kindreds. However, a function has not been assigned to many of the domains that make up these complex proteins and hence, the significance of many sequence variants, including missense mutations, splice-site mutations, and in-frame deletions/insertions, remains unclear. We identified a putative splice site mutation (IVS6-2delA) in BRCA1 in a family attending a Familial Cancer Centre that had a significant history of both breast and ovarian cancer. This sequence variant was not novel but the exact effect on mRNA splicing and hence the biological impact of this sequence variation was unclear and therefore the finding was unable to be used in genetic counseling of the family. Via the construction of novel GFP-based expression fusion constructs, we demonstrated that this sequence variation prevented normal splicing of the BRCA1 transcript. By combining these data with an assessment of the histopathological features of the breast carcinomas in this family and mutation penetrance estimate we were able to conclude that this BRCA1 variant conveyed an increased risk of breast cancer. Hum Mutat 22:86,91, 2003. © 2003 Wiley-Liss, Inc. [source] Mutations in severe combined immune deficiency (SCID) due to JAK3 deficiencyHUMAN MUTATION, Issue 4 2001Luigi D. Notarangelo Abstract During the last 10 years, an increasing number of genes have been identified whose abnormalities account for primary immunodeficiencies, with defects in development and/or function of the immune system. Among them is the JAK3 -gene, encoding for a tyrosine kinase that is functionally coupled to cytokine receptors which share the common gamma chain. Defects of this gene cause an autosomal recessive form of severe combined immunodeficiency with almost absent T-cells and functionally defective B-cells (T,B+ SCID). Herewith, we present molecular information on the first 27 unique mutations identified in the JAK3 gene, including clinical data on all of the 23 affected patients reported so far. A variety of mutations scattered throughout all seven functional domains of the protein, and with different functional effects, have been identified. Availability of a molecular screening test, based on amplification of genomic DNA, facilitates the diagnostic approach, and has permitted recognition that JAK3 deficiency may also be associated with atypical clinical and immunological features. Development of a structural model of the JAK3 kinase domain has allowed characterization of the functional effects of the various mutations. Most importantly, molecular analysis at the JAK3 locus results in improved genetic counseling, allows early prenatal diagnosis, and prompts appropriate treatment (currently based on hematopoietic stem cell transplantation) in affected families. Hum Mutat 18:255,263, 2001. © 2001 Wiley-Liss, Inc. [source] Genetics in Perinatal Nursing: Clinical Applications and Policy ConsiderationsJOURNAL OF OBSTETRIC, GYNECOLOGIC & NEONATAL NURSING, Issue 2 2002Judith A. Lewis PhD Genetics is becoming an important part of perinatal nursing care. The need for genetic counseling and referral may be identified before conception, early in pregnancy, upon the demise of a fetus with an abnormality, or after the birth of an infant with a genetic condition. Perinatal nurses often are present when parents first discover the presence of a genetic condition in their fetus or infant. Women who will be 35 at the time of their infant's birth and women who have family histories of genetic disorders should be offered appropriate screening tests. [source] Mutations in GPIIIa molecule as a cause for Glanzmann thrombasthenia in Indian patientsJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 3 2005S. NAIR Summary.,Background:,Glanzmann thrombasthenia (GT) results from a quantitative or qualitative defect of GPIIb,IIIa complex, the fibrinogen receptor on platelets, which plays a very important role in platelet aggregation. In this report we describe the molecular studies on 22 patients with Glanzmann Thrombasthenia at our institute. Objectives:,The main objective was to identify the mutations present in our GT population in order to establish a strategy for genetic counseling and antenatal diagnosis. Methods:,Twenty-two patients with GT were included in the present study. Complete blood count (CBC), platelet aggregation, flow cytometry, Western blot, single strand conformation polymorphism (SSCP) and denaturing gradient gel electrophoresis (DGGE) were performed in all the patients. The patients showing an abnormal migration pattern in SSCP or DGGE were sequenced further on an automated sequencer. Results:,Of the 22 patients studied, mutations were detected in 12 individuals. Of these, 11 were novel mutations and one mutation Y115C was reported earlier. Flow cytometric analysis showed the absence of receptors in type I GT, highly reduced levels in type II GT and normal levels in type III GT. The DGGE analysis and SSCP analysis of the patients showed different migration patterns. Sequencing was performed in all patients showing an abnormal migration pattern. Of the 22 cases studied mutations could be detected in 12 cases of GT. We could detect six patients with point mutations, four patients with insertions and five patients with deletion mutations. Exon 4 has been found to be the most common site for mutations in our patients. Conclusion:,This study has shown a wide array of mutations present in our GT patients which would be extremely useful in genetic counseling and prenatal diagnosis, essential in preventing these disorders in succeeding generations. [source] Frequency of recombinant and nonrecombinant products of pericentric inversion of chromosome 1 in sperm nuclei of carrier: By FISH techniqueMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 1 2003Tahsin Yakut Abstract Meiotic segregation products of carriers with pericentric inversion are very important for assessing the risk of unbalanced forms and appropriate genetic counseling. We investigated the incidence of recombinant and nonrecombinant products of chromosome 1 with pericentric inversion, in the sperm nuclei of the carrier by using triple color fluorescence in situ hybridization (FISH). The centromere specific and telomere specific probes for chromosome 1 were used. In the segregation analysis, 1,636 sperm nuclei were analyzed; 82.5% of the sperms were including normal or inverted chromosome 1, and the dup(p)/del(q) and del(p)/dup(q) recombinant products in sperm nuclei of our carrier were 8.7 and 7.3%, respectively. The number of recombinant products may be dependent on the formation of an inversion loop, which the number of the formation of chiasmata results in the different number of normal/balanced and recombinant products. The use of FISH, using different probe combination, in sperm nuclei has proved to be an accurate approach to determine the meiotic segregation patterns and could help to better establish a reproductive prognosis and genetic counseling. Mol. Reprod. Dev. 66: 67,71, 2003. © 2003 Wiley-Liss, Inc. [source] The association between mutations in the lysosomal protein glucocerebrosidase and parkinsonism,MOVEMENT DISORDERS, Issue 11 2009John DePaolo BA Abstract A body of work has emerged over the past decade demonstrating a relationship between mutations in glucocerebrosidase gene (GBA), the gene implicated in Gaucher disease (GD), and the development of parkinsonism. Several different lines of research support this relationship. First, patients with GD who are homozygous for mutations in GBA have a higher than expected propensity to develop Parkinson's disease (PD). Furthermore, carriers of GBA mutations, particularly family members of patients with GD, have displayed an increased rate of parkinsonism. Subsequently, investigators from centers around the world screened cohorts of patients with parkinsonism for GBA mutations and found that overall, subjects with PD, as well as other Lewy body disorders, have at least a fivefold increase in the number of carriers of GBA mutations as compared to age-matched controls. In addition, neuropathologic studies of subjects with parkinsonism carrying GBA mutations demonstrate Lewy bodies, depletion of neurons of the substantia nigra, and involvement of hippocampal layers CA2,4. Although the basis for this association has yet to be elucidated, evidence continues to support the role of GBA as a PD risk factor across different centers, synucleinopathies, and ethnicities. Further studies of the association between GD and parkinsonism will stimulate new insights into the pathophysiology of the two disorders and will prove crucial for both genetic counseling of patients and family members and the design of relevant therapeutic strategies for specific patients with parkinsonism. © 2009 Movement Disorder Society [source] The current clinical management of Huntington's disease,MOVEMENT DISORDERS, Issue 11 2008Wendy Phillips MD Abstract Huntington's disease is a neurodegenerative condition, characterized by movement disorders, cognitive decline, and psychiatric disturbance. We review the pharmacological management of the various movement disorders associated with the disease, the cognitive decline and the commonly encountered behavioral disturbances. We discuss the nonclassical features of the disease, important in the management of these patients. Nonpharmacological support including genetic counseling and therapy and the importance of palliative care are also addressed. Finally, experimental approaches that may soon impact upon clinical practice are discussed. © 2008 Movement Disorder Society [source] Central core disease due to recessive mutations in RYR1 gene: Is it more common than described?MUSCLE AND NERVE, Issue 5 2007Patrícia M. Kossugue MS Abstract Central core disease (CCD) is an autosomal-dominant congenital myopathy, with muscle weakness and malignant hyperthermia (MH) susceptibility. We identified two of nine Brazilian CCD families carrying two mutations in the RYR1 gene. The heterozygous parents were clinically asymptomatic, and patients were mildly affected, differing from the few autosomal-recessive cases described previously. Recessive inheritance in CCD may therefore be more common than previously appreciated, which has important implications for genetic counseling and MH prevention in affected families. Muscle Nerve, 2007 [source] The dominantly inherited motor and sensory neuropathies: Clinical and molecular advancesMUSCLE AND NERVE, Issue 5 2006Garth A. Nicholson MB Abstract The rapid advances in the molecular genetics and cell biology of hereditary neuropathy have revealed great genetic complexity. It is a challenge for physicians and laboratories to keep pace with new discoveries. Classification of hereditary neuropathies has evolved from a simple clinical to a detailed molecular classification. However, the molecular classification is not simple to use, as different mutations of the same gene produce a range of phenotypes. The logistics of testing for multiple gene mutations are considerable. This review gives a clinical overview of molecular and clinical advances in the dominant hereditary motor and sensory neuropathies [HMSNs, Charcot,Marie,Tooth (CMT) neuropathy], which account for some 60%,70% of families with CMT. The dominant forms of CMT have cellular mechanisms different from those of recessive forms and are a separate diagnostic challenge, so they are not included in this review. Diagnostic testing requires accurate clinical information and a selective approach to gene screening until the cost of multiple gene mutation screening falls. Accurate molecular diagnosis is critical to genetic counseling. This review concentrates on how molecular information can be used clinically, on how physicians can keep pace with new developments, and on the relevance of this new knowledge to patients. Muscle Nerve, 2006 [source] Using Family History to Assess Women's Cancer Risk in a Parish Nurse SettingNURSING & HEALTH SCIENCES, Issue 2 2006Carol Cherry This health promotion project fulfillled required field study in a graduate public health nursing program. Family history, an important risk factor for many chronic diseases including cancer, is gaining importance as a public health tool. The author used cancer risk assessment expertise to assess women's cancer risk based on family history in two parish settings. Women completed cancer family history using the U.S. Surgeon General's Family Health Portrait. They received pedigree, tailored risk communication and educational materials for cancer prevention/detection. Of 23 women, the majority reported intention to: (i) change behavior to reduce risk; (ii) change screening practice; and (iii) share family history with healthcare providers. One woman at high risk sought formal genetic counseling. Risk information was based on family history only, although multiple factors affect risk. Women's intention to change behavior may not lead to actual change. Population was homogeneous and well educated so results may not be generalizable to other populations. Even though most parish nurses would not have expertise in cancer risk assessment, they can advocate use of the Family Health Portrait. Women respond positively to personalized risk feedback presented in the context of their faith communities. The project facilitated genomic understanding within a public health setting. [source] Pulmonary Tuberculosis and Cutaneous Mycobacterial Infection in a Patient with Incontinentia PigmentiPEDIATRIC DERMATOLOGY, Issue 6 2004Nilgün Senturk M.D. Lupus vulgaris following bacille Calmette-Guérin (BCG) vaccination is a rare entity. Incontinentia pigmenti is an X-linked dominant genodermatosis in which vesicular, verrucous, and pigmented lesions are associated with various developmental defects. There is evidence of altered immunologic reactivity in some patients with incontinentia pigmenti. A 12-year-old girl hospitalized for pulmonary tuberculosis presented with bizarre-shaped brown macules following Blaschko lines on the left deltoid area, compatible with incontinentia pigmenti, which had appeared following BCG vaccination at the age of 7 years. Histopathologic examination found noncaseated granulomas in the dermis. Antituberculous treatment for pulmonary and cutaneous tuberculosis was initiated along with genetic counseling. Immunologic abnormalities have been reported in conjunction with incontinentia pigmenti. Simultaneous occurrence of pulmonary and cutaneous tuberculosis in our patient might be either coincidental or indicate derangements in the cellular immune system. [source] | |||||||||||||