Genetic Counselling (genetic + counselling)

Distribution by Scientific Domains
Distribution within Medical Sciences


Selected Abstracts


Parents of Children with Intellectual Disabilities: Their Expectations and Experience of Genetic Counselling

JOURNAL OF APPLIED RESEARCH IN INTELLECTUAL DISABILITIES, Issue 3 2003
Owen Barr
Background, Following the birth of a child, parents and other family members have to adapt to their new circumstances. This process takes time and can become more complex when the child is suspected or diagnosed as having intellectual disabilities. When a child has a disability, parents often seek answers as to the origin and nature of the condition as part of the adaptation process. For some parents, this will result in genetic investigations and could lead to the provision of personal genetics about the child and parents. Materials and methods, This paper reports a mixed-method project that combined questionnaires prior to and interviews after an appointment with a geneticist. The project sought to identify the expectations and experience of parents who had a child referred to specialist genetics services. Results and conclusions, The findings identify that parents felt largely unprepared for their appointment and reported feelings of failing to maximize the opportunity present. The need for more effective liaison between specialist regional and local primary care and learning disability services is also highlighted. Parents made practical suggestions relevant to all the above services about how they could be better supported at this difficult stage in the adaptation process. [source]


Carrier testing in haemophilia A and B: adult carriers' and their partners' experiences and their views on the testing of young females

HAEMOPHILIA, Issue 3 2008
N. F. DUNN
Summary., This is a descriptive study, which aims to report adult carriers' and their husbands/partners' experiences of carrier diagnosis and their views as to how these issues should be handled for the next generation. Following an initial pilot, 105 carriers and husbands/partners responded to a postal questionnaire. Most of the adult carriers had been tested because either they or their parents wanted to know their carrier status or they had a son diagnosed with haemophilia. The respondents agreed that the main reasons for testing young potential carriers should be either a family history of severe haemophilia or that the young person or her parents wanted to know her status. Forty per cent (35/87) believed the earliest age for carrier testing should be 0,9 years, 44% (38/87) 10,15 years and 16% (14/87) ,16 years. Respondents aged 18,39 years were more likely to be in favour of testing <2 years. If parents and teenagers disagreed, the majority of parents thought that a test should not be forced, consent refused or results withheld. Genetic counselling provides an important opportunity for parents, who want a very early genetic test, to explore their motivations and balance their desire to prepare and protect their daughter with her right to decide as a teenager. [source]


Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation associated with a congenital bilateral absence of vas deferens

INTERNATIONAL JOURNAL OF UROLOGY, Issue 3 2008
Hideo Sakamoto
Abstract: Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations associated with cystic fibrosis have been reported to be rare in Japanese patients with congenital bilateral absence of vas deferens (CBAVD). A 28-year-old Japanese male was referred for infertility. Vas deferens and epididymis were not palpable bilaterally. Semen analyses showed azoospermia with volumes below 2.0 ml. Serum follicle-stimulating hormone value was slightly elevated. Seminal fructose concentration was also very low. Scrotal ultrasonography showed absence of the bodies and tails of the right and left epididymides. Imaging studies showed cystic dysplasia of the right seminal vesicle and agenesis of the left seminal vesicle. A CFTR gene mutation of I556V was found. Recent studies show that prevalence of CFTR gene mutation in Japanese CBAVD patients may be approximately equal to that of the Caucasian population. Genetic counselling may be recommended for any couple attempting assisted reproduction technology when the man has CBAVD. [source]


Lay persons' understanding of the risk of Down's Syndrome in genetic counselling

BJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 6 2001
Hubertus A.A.M. van Vliet
Genetic counselling traditionally expresses risk in proportions (e.g. 1 in 112) rather than as rates (e.g., 8.9 per 1000). The justification for this practice is unclear. To assess the understanding of lay persons of the risk of Down's Syndrome, whether expressed as rates or as proportions, we analysed 589 self-administered questionnaires. Overall, respondents understood rates significantly better than proportions (76.2%vs 72.3% correct, respectively; P=0.03) Evidence from two studies in disparate populations suggests that rates are better understood and thus are the preferred way to explain genetic risk to lay persons. [source]


The molecular genetics of the genodermatoses: progress to date and future directions

BRITISH JOURNAL OF DERMATOLOGY, Issue 1 2003
A.D. Irvine
Summary The Human Genome Mapping Project and allied rapid advances in genetic technology over the past decade have facilitated accurate association of allelic variations in several genes with specific skin phenotypes. Currently the genetic bases of the majority of the more common genodermatoses have been elucidated. In scientific terms this work has been extraordinarily successful and has yielded many new biological insights. These advances, although exciting, have yet to be translated into direct benefit for patients with these diseases. Genetic counselling has been greatly aided by gene identification, by the better understanding of genotype,phenotype correlation and by the disclosure of unexpected genetic mechanisms in some families. Knowledge of the molecular basis of these disorders has also been vital in enabling DNA-based prenatal diagnosis in several conditions and DNA-based preimplantation diagnosis has been used in a selected few. While this successful period of gene mapping is now nearing completion, progress towards the next goal, that of developing therapeutic strategies based on the knowledge of these underlying genetic mechanisms, has proven frustratingly slow. Despite the ready access to the skin compared with solid internal organs, the challenges of cutaneous gene therapy are legion and many technical issues need to be surmounted to enable gene replacement or modification of gene expression to have a useful role in these disorders. In this article we make a comprehensive review of progress to date in gene identification, genotype,phenotype correlation, prenatal diagnosis and cutaneous gene therapy, and we examine future directions for research in this field. [source]


2241: Principles of genetic counselling

ACTA OPHTHALMOLOGICA, Issue 2010
G HALL
Purpose To present the genetic counselling needs of families with inherited eye disease. Methods A presentation on the counselling challenges and ethical dilemmas in genetic services for inherited eye disease using case illustrations and review of research and current literature. Results Genetic counselling for families with inherited eye disease is rapidly advancing with improvements in molecular testing leading to accurate diagnosis and information for families. With increasing patient demand and expectation, families request genetic counselling to understand the inheritance pattern and the risks to themselves and their children. However, the heterogeneity, variable penetrance and overlapping phenotypes make this particularly challenging in genetic eye disease. Genetic counselling is a communication process to provide information about the genetic condition, its inheritance and to facilitate decision-making around genetic testing and reproduction. Genetic counsellors have experience in helping individuals decide and come to terms with results from genetic testing such as pre-symptomatic testing, childhood testing and pre-natal diagnosis. In addition, families are often coping with the psychological burden of progressive blindness and the impact of vision loss and risk to other family members. Recent publications highlight the disparity in specialist service provision for families with inherited eye disease and calls for research and improvements in evidenced-based practice. Conclusion Families with inherited eye disease have complex genetic counselling needs requiring multidisciplinary co-ordination of services for accurate diagnosis, information provision, genetic testing and decision-making, and support and follow-up. [source]


Evaluation of phone-based genetic counselling in African American women using culturally tailored visual aids

CLINICAL GENETICS, Issue 2 2010
T Pal
Pal T, Stowe C, Cole A, Lee J-H, Zhao X, Vadaparampil S. Evaluation of phone-based genetic counselling in African American women using culturally tailored visual aids. Genetic counselling (GC) services for inherited breast and ovarian cancer (HBOC) are underutilized by African American (AA) women. We sought to evaluate factors associated with knowledge gain in a sample of AA women diagnosed with early-onset breast cancer, in whom GC for HBOC was provided, using a culturally targeted genetic counselling aid (GCA). Through a cancer registry-based study, phone-based GC for HBOC was offered to AA women with breast cancer ,50. A questionnaire to assess knowledge about HBOC was completed prior to GC. All women were provided a GCA about HBOC developed by the investigative team for use during the GC session. Following GC, a personalized summary letter was mailed to all study participants and the same knowledge questionnaire was completed. A total of 37 study participants completed the pre- and post-GC knowledge questionnaires with significant gains in knowledge following the GC process (p < 0.0001). Statistically significant factors associated with knowledge gain included earlier stage of diagnosis of breast cancer and education level. Our results indicate that phone-based GC supplemented by a culturally targeted visual aid is an effective means of improving knowledge about HBOC in young AA women with invasive breast cancer. [source]


Clinical features, diagnosis and management of maternally inherited diabetes and deafness (MIDD) associated with the 3243A>G mitochondrial point mutation

DIABETIC MEDICINE, Issue 4 2008
R. Murphy
Abstract Maternally inherited diabetes and deafness (MIDD) affects up to 1% of patients with diabetes but is often unrecognized by physicians. It is important to make an accurate genetic diagnosis, as there are implications for clinical investigation, diagnosis, management and genetic counselling. This review summarizes the range of clinical phenotypes associated with MIDD; outlines the advances in genetic diagnosis and pathogenesis of MIDD; summarizes the published prevalence data and provides guidance on the clinical management of these patients and their families. [source]


A systematic review on the diagnosis and treatment of primary (idiopathic) dystonia and dystonia plus syndromes: report of an EFNS/MDS-ES Task Force

EUROPEAN JOURNAL OF NEUROLOGY, Issue 5 2006
A. Albanese chairman
To review the literature on primary dystonia and dystonia plus and to provide evidence-based recommendations. Primary dystonia and dystonia plus are chronic and often disabling conditions with a widespread spectrum mainly in young people. Computerized MEDLINE and EMBASE literature reviews (1966,1967 February 2005) were conducted. The Cochrane Library was searched for relevant citations. Diagnosis and classification of dystonia are highly relevant for providing appropriate management and prognostic information, and genetic counselling. Expert observation is suggested. DYT-1 gene testing in conjunction with genetic counselling is recommended for patients with primary dystonia with onset before age 30 years and in those with an affected relative with early onset. Positive genetic testing for dystonia (e.g. DYT-1) is not sufficient to make diagnosis of dystonia. Individuals with myoclonus should be tested for the epsilon-sarcoglycan gene (DYT-11). A levodopa trial is warranted in every patient with early onset dystonia without an alternative diagnosis. Brain imaging is not routinely required when there is a confident diagnosis of primary dystonia in adult patients, whereas it is necessary in the paediatric population. Botulinum toxin (BoNT) type A (or type B if there is resistance to type A) can be regarded as first line treatment for primary cranial (excluding oromandibular) or cervical dystonia and can be effective in writing dystonia. Actual evidence is lacking on direct comparison of the clinical efficacy and safety of BoNT-A vs. BoNT-B. Pallidal deep brain stimulation (DBS) is considered a good option, particularly for generalized or cervical dystonia, after medication or BoNT have failed to provide adequate improvement. Selective peripheral denervation is a safe procedure that is indicated exclusively in cervical dystonia. Intrathecal baclofen can be indicated in patients where secondary dystonia is combined with spasticity. The absolute and comparative efficacy and tolerability of drugs in dystonia, including anticholinergic and antidopaminergic drugs, is poorly documented and no evidence-based recommendations can be made to guide prescribing. [source]


ORIGINAL ARTICLE Laboratory science: Spectrum of F8 gene mutations in haemophilia A patients from a region of Italy: identification of 23 new mutations

HAEMOPHILIA, Issue 5 2010
F. RICCARDI
Summary., Haemophilia A (HA) is an X-linked recessive bleeding disorder caused by a lack or decrease of coagulation factor VIII activity. The molecular diagnosis of HA is challenging and a variety of different mutations have been identified throughout the F8 gene. Our aim was to detect the causative mutation in 266 HA patients from Emilia-Romagna region (Italy) and in all suspected carriers. Molecular analysis of F8 in 201 HA patients (152 index cases) was performed with a combination of several indirect and direct molecular approaches, such as long distance polymerase chain reaction, multiplex ligation-dependent probe amplification, denaturing high performance liquid chromatography and direct sequencing. The analysis revealed 78 different mutations, 23 of which were novel, not having been reported in national or international databases. The detection rate was 100%, 86% and 89% in patients with severe, moderate and mild HA, respectively. The information provided by this registry will be helpful for monitoring the treatment of HA patients in Emilia-Romagna and also for reliable genetic counselling of affected families in the future. [source]


Study of mutations in Jordanian patients with haemophilia A: identification of five novel mutations

HAEMOPHILIA, Issue 1 2010
A. AWIDI
Summary., Haemophilia A (HA) is an X-linked recessive bleeding disorder caused by mutations in the factor VIII gene (F8), which encodes factor VIII (FVIII) protein, a plasma glycoprotein, that plays an important role in the blood coagulation cascade. In the present study, our aim was to identify F8 gene mutations in HA patients from Jordan. One hundred and seventy-five HA patients from 42 unrelated families were included in this study. Among these patients, 117 (67%) had severe HA, 13 (7%) had moderate HA and 45 (26%) had mild HA. Severe patients were first tested for intron-22 inversion using long range polymerase chain reaction (PCR), then negative patients were tested for intron-1 inversion using PCR. Sequencing for the entire F8 gene was performed for all severe HA patients who were found negative for intron-22 and -1 inversions and it was also performed for moderate and mild HA patients. HA causative mutations were identified in all patients. Intron-22 and -1 inversions were detected in 52% and 2% of families respectively. Beside these two mutations, 19 different mutations were identified, which include 15 missense and four frameshift mutations. Five novel mutations were identified including one frameshift and four missense mutations. No large deletions or nonsense mutations were detected in patients who participated in this study. Only 17 patients with severe HA were found positive for FVIII inhibitors. The data presented will play an important role for genetic counselling and health care of HA patients in Jordan. [source]


Is informed choice in genetic testing a different breed of informed decision-making?

HEALTH EXPECTATIONS, Issue 2 2001
A discussion paper
Traditionally genetic counselling has promoted a non-directive approach to patients' decision-making but the feasibility of this has been questioned. Unlike most branches of medicine, which are shifting away from a paternalistic model, genetic counselling is approaching shared decision-making from a different perspective. There are certain features of genetic counselling and genetic testing which may complicate the drive towards shared decision-making and informed choice: 1. Genetic test results can have broader implications than non-genetic test results. 2. Genetic test results may be perceived by the patient differently to non-genetic test results. 3. Carrier status for autosomal recessive conditions may be difficult for patients to conceptualize. 4. Decisions in genetic counselling are often multiple and sequential. 5. Most information in genetic counselling is based on probabilities and uncertainties. Each of these features is discussed in relation to achieving shared decision-making in genetic testing and the implications for genetic counsellors are described. The points raised, however, have broader implications for medicine as several of the features, although central to genetic testing, are not entirely unique. Lessons learnt from genetic testing and genetic counselling in achieving shared decision-making could help develop methods of promoting informed choice in other medical arenas such as cancer screening. [source]


The pathology of hypertrophic cardiomyopathy

HISTOPATHOLOGY, Issue 5 2004
S E Hughes
Sudden cardiac death (SCD) is devastating at any age, but even more so when the individual affected is young and asymptomatic, and the death is entirely unexpected. SCD is a catastrophic complication of hypertrophic cardiomyopathy (HCM) and may be the first manifestation of this disease. HCM is an inherited intrinsic disease of the myocardium characterized by left ventricular hypertophy without chamber dilatation, in the absence of either a systemic or other cardiac disease, which may cause a similar magnitude of hypertrophy. HCM may be a clinically silent disease. Indeed, the pathologist may be the first to encounter a case of HCM at autopsy. HCM has wide-ranging implications for affected families, who will require cardiac screening and genetic counselling even if mutations are not known. Therefore, prompt and accurate diagnosis of HCM is vital. This review article will focus on the pathological diagnosis of HCM, recent advances in the genetics of this disease, and common pitfalls which may arise, leading to diagnostic uncertainty. [source]


An interplay of alleviating mutations in the clinical phenotype of ,-thalassaemia intermedia

INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 6 2004
A. NADKARNI
Summary Prediction of a , -thalassaemia major phenotype from the , -genotype is generally relatively straightforward. However, despite the ability to accurately define the , -thalassaemia mutations, prediction of a , -thalassaemia intermedia phenotype from the genotype sometimes remains problematic and this has important implications in genetic counselling and prenatal diagnosis. We report a 11-year-old Indian male child with a thalassaemia intermedia phenotype. , -Globin gene analysis of the family showed that he was a compound heterozygote with the ,88 (C,T) ,+ -mutation and the IVS1 nt 130 (G,C) ,0 -mutation. Both these mutations are rare among Indians. The propositus was also found to be heterozygous for the XmnI polymorphism and had a normal , -genotype. In this family interplay of two alleviating mutations (a milder promoter mutation along with a gene for raised HbF) might have synergistically compensated for lack of globin chains in the patient. Hence, the nature of the , -genotype as well as the knowledge of the presence or absence of alleviating factors will help the clinician to decide whether early commencement of a regular transfusion regime is necessary. [source]


Evaluation of an automated screening assay for von Willebrand Disease Type 2N

INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 6 2002
S. L. Taylor
Summary Evaluating the factor VIII (FVIII) binding activity of von Willebrand factor (VWF) is an important step in the diagnostic work-up of families affected by apparent mild haemophilia A. In von Willebrand's disease (VWD) type 2N (Normandy), mutations at the N-terminal end of the mature VWF subunit gene prevent the binding of FVIII. Individuals heterozygous for type 2N VWD are generally asymptomatic. Homozygotes and compound heterozygotes present with a clinical picture which mimics haemophilia A, with a markedly reduced FVIII : C activity and VWF within the normal range, but instead of exhibiting X-linked inheritance they show an autosomal recessive inheritance pattern. The distinction between haemophilia A and VWD type 2N has important implications for therapy and genetic counselling. We present a highly specific enzyme-linked immunosorbent assay screening method for the Normandy variant, which measures VWF : FVIII binding activity in parallel with VWF antigen, using monoclonal capture and detection antibodies. The assay is fully automated using a robotic microtitre plate processor, requiring minimal user intervention and providing the capacity to screen large numbers of patients. [source]


Haemoglobin H disease due to (,,,SEA) ,-globin gene deletion and ,2-codon 30 (,GAG) mutation: a family study

INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 5 2001
S.K. Ma
A Chinese family in which two siblings suffer from haemogloblin (Hb) H disease due to (,,,SEA) ,-globin gene deletion and ,2-codon 30 (,GAG) mutation is described. Both siblings are transfusion-independent and have survived to adulthood. In contrast to previous report of hydrops fetalis associated with ,-,-thal-1 and ,2-codon 30 (,GAG) mutation, the ,-globin genes are intact in the two siblings, which most probably alleviates the ,-chain excess and protects the fetus from severe anaemia. Correlation of genotype with phenotype in Hb H disease is important for genetic counselling, especially in the antenatal setting. [source]


The Van der Woude syndrome: a case report and review of the literature

JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 5 2004
J Dissemond
ABSTRACT The Van der Woude syndrome is a rare autosomal dominant developmental malformation usually associated with bilateral lower lip pits. These congenital lip pits appear clinically as a malformation in the vermilion border of the lip, with or without excretion. As a genetic defect has been identified as a microdeletion of chromosome bands 1q32,q41, genetic counselling of patients may be considered. A nonsense mutation in the interferon regulatory factor-6 (IRF-6) is discussed as a pathogenic relevant factor. Therapeutic intervention is generally not necessary, although surgical excision is especially indicated in patients with recurrent inflammation. Physicians should be aware of the Van der Woude syndrome because it has been reported to be associated with a variety of malformations or other congenital disorders. [source]


Theme-oriented discourse analysis of medical encounters

MEDICAL EDUCATION, Issue 6 2005
Celia Roberts
Approach, Theme-oriented discourse analysis looks at how language constructs professional practice. Recordings of naturally occurring interactions are transcribed and combined with ethnographic knowledge. Analytic themes drawn primarily from sociology and linguistics shed light on how meaning is negotiated in interaction. Detailed features of talk, such as intonation and choice of vocabulary, trigger inferences about what is going on and being talked about. These affect how interactants judge each other and decisions are made. Interactions also have larger rhetorical patterns used by both patients and doctors to persuade each other. Examples, Two settings are used to illustrate this approach: genetic counselling and primary care consultations in multilingual areas. In genetic counselling, interactions are organised around the tension between the risks of knowing and the risks of occurrence. This can lead to a ,rhetorical duel' between health professionals and patients and their families. In intercultural primary care settings, talk itself may be the problem when interpretive processes cannot be taken for granted. Even widely held models of good practice can lead to misunderstandings under these conditions. Conclusion, Through discourse analysis, the talk under scrutiny can be slowed down to show the interpretive processes and overall patterns of an activity. Discourse analysts and health professionals, working together, can look at problems in new ways and develop interventions and tools for a better understanding of communication in medical life. [source]


Variability of immunodeficiency associated with ataxia telangiectasia and clinical evolution in 12 affected patients

PEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 7 2005
G. Claret Teruel
Ataxia telangiectasia (AT) is an infrequent condition, which is difficult to diagnose in children. The objective was to describe the evolution of all affected patients controlled in our hospital and to highlight the keys for an early diagnosis considering the variability of immunological disorders. The present study is a retrospective review of all patients diagnosed and controlled of AT in our hospital. Twelve patients were found, including two couples of siblings. The most frequent reason for consultation was unstable gait. Seven patients suffered repeated infections, being pneumonia the most frequent cause of infection, followed by sinusitis. One of the patients developed Burkitt's lymphoma, and another patient, Hodgkin's lymphoma, which caused the death of the patient at the age of 11. A couple of siblings aged 17 and 22 years developed insulin-resistant diabetes mellitus. The most frequent immunity disorders were the IgG deficiency and the decrease of T lymphocytes. Seven patients were treated with non-specific gamma-globulin. By the end of the follow-up, 8 patients (ages ranged 7 to 12 years) lost gait. Molecular genetic testing was conducted in patients who are still cared for in our hospital. Clinical suspicion of this entity will lead to an early diagnosis, the treatment of complications, and to provide genetic counselling for the families. [source]


A novel mutation of the ,-globin gene promoter (,102 C>A) and pitfalls in family screening

AMERICAN JOURNAL OF HEMATOLOGY, Issue 12 2007
Patricia Aguilar-Martinez
We describe a family with ,-thalassemia in which several pitfalls of genetic diagnoses were present. These include coherent family phenotypes with discrepancies in molecular findings because of nonpaternity, and a false ,-globin gene homozygous genotype due to a large deletion in the second locus. These findings underline the difficulties of family genetic studies and the need for tight relationship between professionals involved in laboratory studies and those in-charge of the clinical follow-up and genetic counselling. In this family, we also report a new silent ,-thalassemia mutation, ,102 (C>A), in the distal CACCC box of the ,-globin gene promoter. Am. J. Hematol., 2007. © 2007 Wiley-Liss, Inc. [source]


Application of QF-PCR for the prenatal assessment of discordant monozygotic twins for fetal sex

PRENATAL DIAGNOSIS, Issue 7 2007
F. J. Fernández-Martínez
Abstract Objective To establish the utility of quantitative fluorescent polymerase chain reaction (QF-PCR) in order to determine the zygosity of multiple pregnancies, as well as to define the origin of the most frequent aneuploidies in amniotic fluid samples. Methods We describe the case of a monochorionic (MC) diamniotic (DA) pregnancy with phenotypically discordant twins (nuchal cystic hygroma and non-immune hydrops in twin A and no anomalies in twin B). QF-PCR was performed for rapid prenatal diagnosis in uncultured amniocytes and subsequently in cultured cells. Polymorphic markers for chromosomes X, Y, 13, 18 and 21 were used for determination of zygosity as well as sex chromosome aneuploidy. Results Twin A showed a Turner Syndrome (TS) mosaicism pattern by QF-PCR in uncultured amniocytes. The monozygotic origin of the pregnancy was determined. Interphase fluorescence in situ hybridization (I-FISH) in this sample showed a mosaicism X0/XY (83/17%). Cytogenetic analysis revealed a 45,X0 karyotype in twin A and a 46,XY karyotype in twin B. Conclusions QF-PCR is a reliable tool for the determination of the zygosity independently of the chorionicity and the fetal sex in case of twin pregnancy. Testing both direct and cultured cells can provide useful results for genetic counselling in chromosomal mosaicisms. Copyright © 2007 John Wiley & Sons, Ltd. [source]


Attitudes to prenatal and preimplantation diagnosis in Saudi parents at genetic risk

PRENATAL DIAGNOSIS, Issue 11 2006
Ayman Alsulaiman
Abstract Background Prenatal diagnosis (PND) is only available for severe abnormality in Saudi Arabia, and preimplantation genetic diagnosis (PGD) has been proposed as a valuable alternative. The acceptability of PGD is unexplored, and may ultimately determine the value of this technology in Saudi Arabia. This study reports attitudes towards PND and PGD of Saudi couples offered genetic counselling following the birth of a child with a single gene or chromosomal condition. Methods Thirty couples attending the King Faisal Specialist Hospital and Research Centre in Riyadh were interviewed using a semi-structured questionnaire. One couple had previous experience of PND and none had experience of PGD or IVF. Results Eight of the 30 couples (27%) would only accept PGD; four (13%) only PND; three (10%) either technology; the remainder would accept neither test, or were unsure. The main concerns of those who would accept neither technology were related to personal religious views. Specific concerns about PGD related to the IVF procedure, the risk of multiple pregnancies, the chance of mistakes and the chance of not getting pregnant. A high proportion of couples (six out of seven; 86%) who had a child with thalassaemia expressed interest in PGD, and all would be prepared to use technology to avoid having an affected child. Views were more mixed for the other conditions. Conclusion PGD is acceptable to many couples and for some, it represents a valuable alternative to PND. However, parents' concerns are complex, and the acceptability of different reproductive technologies must be established on an individual basis. Copyright © 2006 John Wiley & Sons, Ltd. [source]


Identification, characterization and clinical implications of two markers detected at prenatal diagnosis

PRENATAL DIAGNOSIS, Issue 10 2006
Rosário Pinto Leite
Abstract Objectives Marker chromosomes are relatively rare in the general population as its identification at prenatal diagnosis. In this article, we identified and characterized two de novo supernumerary marker chromosomes in a mosaic form at prenatal diagnosis. Methods The two cases presented were detected during prenatal diagnosis at 17 and 15 weeks of gestation. The analyses were performed due to the advanced maternal age. In both cases, parent's karyotypes were normal. The identification of the marker chromosomes was possible by FISH techniques. Results One marker chromosome was derived from chromosome 5 and the other from chromosome 6. Both children are well at the moment. Conclusion The two cases described in the present paper, join to the ones already described in the literature. However these results are the first ones without any phenotypical anomalies, at least until the present. Every new characterization of marker chromosomes at prenatal diagnosis should be reported for determining a genotype-phenotype correlation, and thus be used for genetic counselling and risk evaluation. Copyright © 2006 John Wiley & Sons, Ltd. [source]


Trisomy 15 mosaicism owing to familial reciprocal translocation t(1;15): implication for prenatal diagnosis

PRENATAL DIAGNOSIS, Issue 6 2006
Paolo Prontera
Abstract We describe a 4-year-old female child with severe global mental retardation, myoclonic epilepsy, proximal hypotonia and dysmorphisms, whose prenatal diagnosis following amniocentesis revealed a constitutional female karyotype carrying a t(1;15)(q10;p11) familial reciprocal translocation. Post-natal high-resolution karyotype, Fluorescence in situ hybridization (FISH) screening for subtelomeric rearrangements, VNTR search for UPD15 in the blood and fibroblast, and WCP1 and 15 in the mother, failed to provide an explanation for the complex clinical phenotype of the proband. Since the pachytene configuration of the translocated chromosomes defines a high probability of 3:1 segregation, an extensive workup was undertaken to look for a possibly cryptic mosaicism. Four percent of the cells with trisomy 15 was found in the peripheral blood lymphocytes examined by classical cytogenetic technique and interphase FISH analysis. The clinical features associated with cryptic trisomy 15 mosaicism and the problems concerning prenatal diagnosis and genetic counselling for carriers of translocations at high risk of 3:1 segregation are discussed. Copyright © 2006 John Wiley & Sons, Ltd. [source]


Prenatal diagnosis of jumping translocation involving chromosome 22 with ultrasonographic findings

PRENATAL DIAGNOSIS, Issue 11 2005
Halil Aslan
Abstract We report on the prenatal diagnosis and ultrasonographic findings of a second-trimester fetus with jumping translocation involving chromosome 22. A 28-year-old gravida 2, partus 1, Turkish woman was referred for genetic counselling and ultrasonographic examination at 18 weeks' gestation because of a high risk of trisomy 21 in triple test. Prenatal ultrasonography showed tetralogy of Fallot with a diverticular dilatation of the pulmonary artery, flattened brow, complete absence of the right upper limb, hypospadias, oligodactyly (three digits) in left hand and in both feet, and hyperechogenic abdominal foci. Amniocentesis revealed a karyotype of 46,XY[4]/46,XY,,8,+ der(8),t(8;22)(q24.3;q11.21)[2]/45, XY,,22,,8,+ der(8)t(8;22)(q24.3;q11.21)[22]/45,XY,,22,,5,+ der(5)t(5;22)(q35.3;q11.21)[44]. A C-banding and FISH study with a specific centromeric probe (D14Z1/D22Z1) for chromosome 22 was made. In our case, partial monosomy for the regions 22q11.21,22pter, 8q24.3,8qter and 5q35.3,5qter may partially explain the fetal malformations. Copyright © 2005 John Wiley & Sons, Ltd. [source]


Molecular and cytogenetic characterization of extra-structurally abnormal chromosomes (ESACs) found prenatally: outcome and follow-up

PRENATAL DIAGNOSIS, Issue 12 2003
E. Marchina
Abstract A 40-year-old woman underwent amniocentesis at 15.3 weeks of gestation. Chromosome analysis performed using QFQ, DA-DAPI and CBG banding revealed two de novo extra-chromosomal markers (ESACs) in 11 of the 16 colonies analysed. Fluorescence in situ hybridization (FISH) showed that both chromosomes came from the Yq11.22.1 region of the Y chromosome. PCR analysis of genes and STS localized on the Y chromosome excluded the Yp presence specifically of the SRY gene, and most of the euchromatic region of Yq. After extensive genetic counselling and considering both laboratory and second-level ultrasound data, the couple decided to continue the pregnancy. At 37.4 weeks of gestational age, a girl weighing 2750 g was born with an Apgar score of 9/10. A blood sample taken from the umbilical cord showed three cellular lines:mos47,XX, +mar1 ish.der (Y)(wcpY+) [21%]/48,XX, +mar1 ish.der (Y)(wcpY+), +mar2 ish.der (Y)(wcpY+) [41%]/46,XX [38%]. One year after birth, the baby was developing normally and had normal psychomotorial activity. Copyright © 2003 John Wiley & Sons, Ltd. [source]


Prenatal diagnosis of female monozygotic twins discordant for Turner syndrome: implications for prenatal genetic counselling

PRENATAL DIAGNOSIS, Issue 8 2002
B. Gilbert
Abstract We describe a set of monozygotic (MZ) female twins, one of whom presented with a typical Turner syndrome (TS) phenotype and the other a normal female phenotype. Prenatal fetal ultrasonographic examination showed a monochorial diamniotic pregnancy with a hygroma colli and growth delay in Twin A and no anomalies in Twin B. Karyotypic analysis performed on fetal blood samples demonstrated a 46,XX/45,X (23/2) mosaicism in Twin A and a normal 46,XX chromosome constitution in Twin B. At birth, Twin A presented with a typical TS and Twin B had a normal female phenotype. Postnatal cytogenetic investigation of blood lymphocytes showed the same 46,XX/45,X mosaicism in both twins: 46,XX/45,X (40/7) in Twin A and 46,XX/45,X (40/5) in Twin B. Further investigations at the age of 10,months showed in Twin A a 46,XX/45,X (98/2) mosaicism in lymphocytes and 100% of 45,X (50 analysed cells) in fibroblasts, and in Twin B a normal 46,XX (100 analysed cells) chromosome constitution in lymphocytes but a mild 46,XX/45,X (78/2) mosaicism in fibroblasts. Monozygosity was confirmed by molecular analysis. To our knowledge, this is the first report of prenatal diagnosis of MZ female twins discordant for TS. Review of reported sets of MZ female twins (eight cases) or triplets (one case) discordant for TS shows, as in the present case, that the phenotype correlates better with the chromosomal distribution of mosaicism in fibroblasts than in lymphocytes. In the blood of MZ twins chimerism may modify the initial allocation of the mosaicism. These results suggest that, in cases of prenatal diagnosis of MZ female twins discordant for TS, the phenotype of each twin would be better predicted from karyotype analysis of cells from amniotic fluid than from fetal blood. Copyright © 2002 John Wiley & Sons, Ltd. [source]


Hydrops fetalis in three male fetuses of a female with incontinentia pigmenti

PRENATAL DIAGNOSIS, Issue 12 2001
Andreas Dufke
Abstract Objectives Careful investigation of hydrops fetalis (HF) is important with regard to genetic counselling and prenatal diagnosis. HF is known to be associated with various genetic disorders. To date there has been only one report of a male fetus in whom incontinentia pigmenti (IP) was associated with generalised oedema. We describe a family who had a girl with clinical signs of IP after three consecutive miscarriages of three male fetuses due to HF. Results Molecular genetic analysis showed a mutation in the NEMO/IKK, gene in the girl and the mother, which confirmed the diagnosis of IP in both cases. In the two fetuses that could be investigated, inheritance of the affected maternal X chromosome could be demonstrated retrospectively by linkage analysis. Conclusion The present findings suggest that IP might be an X-linked dominant trait causing HF in male fetuses. In cases of recurrent HF in male fetuses, minimal signs of IP in the maternal line should therefore be carefully investigated in order to be able to perform mutational analysis and to offer appropriate genetic counselling. Copyright © 2001 John Wiley & Sons, Ltd. [source]


Identification of a small supernumerary marker chromosome, r(2)(p10q11.2), and the problem of determining prognosis

PRENATAL DIAGNOSIS, Issue 10 2001
N. Villa
Abstract The identification of small supernumerary marker chromosomes (SMCs) and the elucidation of their clinical significance remain two of the problems in classical human cytogenetics. We observed a small supernumerary ring in amniotic fluid cell cultures and identified its origin as r(2)(p10q11.2) and its extent by means of fluorescent in situ hybridisation (FISH). Uniparental disomy (UPD) was excluded by microsatellite analysis using polymorphic markers localised in the same region. On the basis of normal ultrasonographic checks, the patient decided to continue the pregnancy. A normal female was delivered at term and subsequent neonatal follow-ups confirmed the normal phenotype and development. In the present case, genetic counselling was not helpful because of the absence of reference cases. Detailed characterisation made it possible to correlate the normal baby phenotype with the trisomic 2p10-2q11.2 genomic region. Further molecular cytogenetic investigations of SMCs classified by DNA content and pregnancy outcome data should improve genetic counselling and risk evaluation. Copyright © 2001 John Wiley & Sons, Ltd. [source]


The counsellees' view of an unclassified variant in BRCA1/2: recall, interpretation, and impact on life

PSYCHO-ONCOLOGY, Issue 8 2008
Joël Vos
Abstract Objective: Unclassified variants (UVs, variants of uncertain clinical significance) are found in 13% of all BRCA1/2 mutation analyses. Little is known about the counsellees' recall and interpretation of a UV, and its psychosocial/medical impact. Method: Retrospective semi-structured interviews with open questions and five-point Likert scales were carried out in 24 counsellees who received a UV result 3 years before (sd=1.9). Results: Sixty-seven percent (16/24) recalled the UV result as a non-informative DNA result; 29% recalled a pathogenic result. However, 79% of all counsellees interpreted the UV result as a genetic predisposition for cancer. Variations in recall and interpretation were unexplained by demographics, cancer history of themselves and relatives, and communication aspects of UV disclosure. Sixty-seven percent perceived genetic counselling as completed, whereas 71% expected to receive new DNA information. Although most counsellees reported that UV disclosure had changed their lives in general little, one in three counsellees reported large changes in specific life domains, especially in surveillance behavior and medical decisions. Ten out of 19 participants who interpreted the UV as pathogenic had undergone preventive surgery against none of the 5 counsellees who interpreted the UV as non-informative. Conclusion: Counsellors and researchers need to address discrepancies between the counsellees' factual recall and their subjective interpretation of non-informative BRCA1/2-test results. Copyright © 2007 John Wiley & Sons, Ltd. [source]