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Autosomal Dominant Inheritance (autosomal + dominant_inheritance)

Distribution by Scientific Domains

Medical Sciences	77%
Life Sciences	22%

Distribution within Medical Sciences

Neurology	48%
Dermatology	32%

Selected Abstracts

Autosomal Dominant Inheritance of Centrotemporal Sharp Waves in Rolandic Epilepsy Families

EPILEPSIA, Issue 12 2007
Bhavna Bali
Summary Purpose: Centrotemporal sharp (CTS) waves, the electroencephalogram (EEG) hallmark of rolandic epilepsy, are found in approximately 4% of the childhood population. The inheritance of CTS is presumed autosomal dominant but this is controversial. Previous studies have varied considerably in methodology, especially in the control of bias and confounding. We aimed to test the hypothesis of autosomal dominant inheritance of CTS in a well-designed family segregation analysis study. Methods: Probands with rolandic epilepsy were collected through unambiguous single ascertainment. Siblings in the age range 4,16 years underwent sleep-deprived EEG; observations from those who remained awake were omitted. CTS were rated as present or absent by two independent observers blinded to the study hypothesis and subject identities. We computed the segregation ratio of CTS, corrected for ascertainment. We tested the segregation ratio estimate for consistency with dominant and recessive modes of inheritance, and compared the observed sex ratio of those affected with CTS for consistency with sex linkage. Results: Thirty siblings from 23 families underwent EEG examination. Twenty-three showed evidence of sleep in their EEG recordings. Eleven of 23 recordings demonstrated CTS, yielding a corrected segregation ratio of 0.48 (95% CI: 0.27,0.69). The male to female ratio of CTS affectedness was approximately equal. Conclusions: The segregation ratio of CTS in rolandic epilepsy families is consistent with a highly penetrant autosomal dominant inheritance, with equal sex ratio. Autosomal recessive and X-linked inheritance are rejected. The CTS locus might act in combination with one or more loci to produce the phenotype of rolandic epilepsy. [source]

Neurofibromatosis Type I as a Model of Autosomal Dominant Inheritance

PEDIATRIC DERMATOLOGY, Issue 5 2001
C.G.C., Lucie Dupuis M.Sc.
No abstract is available for this article. [source]

Family and segregation studies: 411 Chinese children with primary nocturnal enuresis

PEDIATRICS INTERNATIONAL, Issue 5 2007
QING WEI WANG
Abstract Background: The aim of the present paper was to determine the incidence of primary nocturnal enuresis (PNE) among relatives of Chinese children with PNE, the inheritance pattern, and to identify the characteristics of PNE with positive family history. Methods: From July 2003 to June 2004, an epidemiological survey on PNE children was carried out by self-administered questionnaires to parents of 5,18-year-old Chinese students in Henan Province, central China. A detailed family history was recorded in order to determine the presence of familial PNE as defined as any close relative with PNE beyond the age of 5 years. Results: The response rate was 88% (10 383/11 799), and 411 children (235 boys and 176 girls) with PNE were identified. A positive family history was found in 94 families (22.87%) of 411 probands with PNE, including 48.94% of fathers, 8.51% of mothers, 6.38% of both parents, 6.38% of the siblings and 29.79% of grandfathers or (and) mothers. Among the probands the ratio of male to female was 1.3:1 excluding sex-linked inheritance. Autosomal dominant inheritance was in 14.60%, and autosomal recessive inheritance was consistent in 1.46% of families. In PNE children with positive family history, the proportion of adolescents, with associated daytime symptoms, marked PNE and seeking professional help were significantly higher than those in PNE children without positive family history. Conclusions: PNE has a significant family clustering, and all modes of inheritance can occur in different families on the basis of a formal genetic analysis. Those with positive family history often manifest marked PNE, and have daytime symptoms. [source]

Familial monozygotic twinning: A report of seven pedigrees,

AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 2 2009
Geoffrey Machin
Abstract Seven families contained 19 MZ twin pairs (2.7 pairs/family), diagnosed by low-stringency variable number tandem repeats in DNA from placental tissue or blood. Chorion status was known in 10 pairs, 6 dichorionic, 4 monochorionic. Sex ratio was equal. Autosomal dominant inheritance is apparent. © 2009 Wiley-Liss, Inc. [source]

Familial paroxysmal exercise-induced dystonia: atypical presentation of autosomal dominant GTP-cyclohydrolase 1 deficiency

DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 6 2010
RUSSELL C DALE
Paroxysmal exercise-induced dystonia (PED) is one of the rarer forms of paroxysmal dyskinesia, and can occur in sporadic or familial forms. We report a family (male index case, mother and maternal grandfather) with autosomal dominant inheritance of paroxysmal exercise-induced dystonia. The dystonia began in childhood and was only ever induced after many minutes of exercise, and was never present at rest, or on initiation of movements. In addition, family members suffered restless legs syndrome (RLS), depression, and adult-onset Parkinsonism. The index case had low cerebrospinal fluid neurotransmitters and pterins. The PED and RLS stopped on initiation of l -Dopa therapy. Both live family members were found to have a nonsense mutation (p.E84X) in exon 1 of the GTP-cyclohydrolase 1 (GCH-1) gene. We propose that GCH-1 mutations should be considered a genetic cause of familial PED, especially if additional clinical features of monoaminergic deficiency are present in affected individuals. [source]

An autosomal dominant genetically heterogeneous variant of rolandic epilepsy and speech disorder

EPILEPSIA, Issue 6 2008
Steven L. Kugler
Summary We report a three generation pedigree with 11 of 22 affected with a variant form of rolandic epilepsy, speech impairment, oromotor apraxia, and cognitive deficit. The core features comprised nocturnal rolandic seizures, interictal centrotemporal spike waves with early age of onset and late age of offset. The transmission of the phenotype was consistent with autosomal dominant inheritance, with variable expressivity but no evidence of anticipation. We found evidence that the seizure and speech traits may be dissociated. No abnormalities were found by cytogenetic analysis. Linkage analysis excluded loci at 11p, 15q, 16p12, and Xq22 for related phenotypes, suggesting genetic heterogeneity. [source]

Autosomal Dominant Inheritance of Centrotemporal Sharp Waves in Rolandic Epilepsy Families

Autosomal Dominant Early-onset Cortical Myoclonus, Photic-induced Myoclonus, and Epilepsy in a Large Pedigree

EPILEPSIA, Issue 10 2006
Elena Gardella
Summary:,Purpose: Cortical tremor, a form of rhythmic cortical myoclonus (rhythmic CM), and epilepsy have been described in families with autosomal dominant inheritance. Linkage analyses revealed two putative loci on chromosome 2p and 8q. Clinical photosensitivity was not a prominent feature in such families. We describe a large Italian family with rhythmic CM, photosensitivity, and epilepsy. Methods: Twenty-three individuals of a five-generation family were studied. Linkage analyses for the loci on chromosome 2p11.1 and 8q23.3 were performed. Results: Of the 23 studied family members, 16 were affected. Rhythmic CM of childhood onset was present in all 16 individuals (onset ranging from 3 to 12 years), was associated with photic-induced myoclonic jerks in seven, and with epileptic seizures in six (onset ranging from 23 to 34 years). Five children of the V generation manifested also episodes of arousal with generalized tremor in early infancy ("tremulous arousals"). Jerk-locked back-averaging of rhythmic CM of six affected individuals, documented a premyoclonic EEG correlate. C-reflex at rest was present in two affected adults. Linkage analyses excluded mapping to the 2p11.1 and 8q23.3 loci. Conclusions: Clinical variability and severity of the phenotypes in this family are in line with those of previously described pedigrees with autosomal dominant cortical myoclonus and epilepsy. In this family, a progression of symptoms was found: rhythmic CM and tremulous arousals occurred in childhood, whereas visually induced manifestations and epileptic seizures occurred during adolescence,adulthood. Exclusion of linkage to the two known loci is consistent with genetic heterogeneity of such familial clustering of symptoms. [source]

Malignant pheochromocytoma with progressive paraparesis in von Hippel,Lindau disease

EUROPEAN JOURNAL OF NEUROLOGY, Issue 4 2000
R. Mössner
Pheochromocytomas are a feature of the von Hippel,Lindau disease spectrum, a multisystem disorder of autosomal dominant inheritance. Pheochromocytomas are, however, observed during life with a lower frequency than other features of this disease, such as retinal angiomas, haemangioblastomas of the CNS, and renal carcinomas. We present the highly unusual case of a patient who required an emergency operation for an intradural extramedullary thoracic tumour which was clinically suggestive initially of neurinoma. We present evidence from NMR, histological and isotope scan investigations of this being a pheochromocytoma metastasis and of an additional right-sided paraganglioma at the same height. A detailed history revealed that this patient had suffered from four other pheochromocytomas and two other paragangliomas, in addition to retinal angiomatosis of von Hippel,Lindau disease. This case is extraordinary due to (i) the unusual site of the metastasis, (ii) the neurological requirement for an emergency operation of pheochromocytoma, (iii) metastasis of pheochromocytoma in von Hippel,Lindau disease (only eight previous cases), and (iv) the number of recurrent pheochromocytomas. It clearly demonstrates the necessity for frequent and life-long follow-up in von Hippel,Lindau disease. [source]

Molecular analysis of the A322D mutation in the GABAA receptor ,1 -subunit causing juvenile myoclonic epilepsy

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2005
Klaus Krampfl
Abstract Juvenile myoclonic epilepsy (JME) belongs to the most common forms of hereditary epilepsy, the idiopathic generalized epilepsies. Although the mode of inheritance is usually complex, mutations in single genes have been shown to cause the disease in some families with autosomal dominant inheritance. The first mutation in a multigeneration JME family has been recently found in the ,1 -subunit of the GABAA receptor (GABRA1), predicting the single amino acid substitution A322D. We further characterized the functional consequences of this mutation by coexpressing ,1 -, ,2 - and ,2 -subunits in human embryonic kidney (HEK293) cells. By using an ultrafast application system, mutant receptors have shown reduced macroscopic current amplitudes at saturating GABA concentrations and a highly reduced affinity to GABA compared to the wild-type (WT). Dose,response curves for current amplitudes, activation kinetics, and GABA-dependent desensitization parameters showed a parallel shift towards 30- to 40-fold higher GABA concentrations. Both deactivation and resensitization kinetics were considerably accelerated in mutant channels. In addition, mutant receptors labelled with enhanced green fluorescent protein (EGFP) were not integrated in the cell membrane, in contrast to WT receptors. Therefore, the A322D mutation leads to a severe loss-of-function of the human GABAA receptor by several mechanisms, including reduced surface expression, reduced GABA-sensitivity, and accelerated deactivation. These molecular defects could decrease and shorten the resulting inhibitory postsynaptic currents (IPSCs) in vivo, which can induce a hyperexcitability of the postsynaptic membrane and explain the occurrence of epileptic seizures. [source]

Identification of eight novel glucokinase mutations in Italian children with maturity-onset diabetes of the young,,

HUMAN MUTATION, Issue 4 2003
Vilma Mantovani
Abstract Maturity-onset diabetes of the young (MODY) is a clinically heterogeneous group of disorders characterized by early onset non-insulin-dependent diabetes mellitus, autosomal dominant inheritance, and primary defect in the function of the beta cells of the pancreas. Mutations in the glucokinase (GCK) gene account for 8%,56% of MODY, with the highest prevalences being found in the southern Europe. While screening for GCK mutations in 28 MODY families of Italian origin, we identified 17 different mutations (corresponding to 61% prevalence), including eight previously undescribed ones. The novel sequence variants included five missense mutations (p.Lys161Asn c.483G>C in exon 4, p.Phe171Leu c.511T>C in exon 5 and p.Thr228Ala c.682A>G, p.Thr228Arg c.683C>G, p.Gly258Cys c.772G>T in exon 7), one nonsense mutation (p.Ser383Ter c.1148C>A in exon 9), the splice site variant c.1253+1G>T in intron 9, and the deletion of 12 nucleotides in exon 10 (p.Ser433underscore;Ile436del c.1298_1309del12). Our study indicates that mutations in the GCK/MODY2 gene are a very common cause of MODY in the Italian population and broadens our knowledge of the naturally occurring GCK mutation repertoire. © 2003 Wiley-Liss, Inc. [source]

Analysis of a non-functional HNF-1, (TCF1) mutation in Japanese subjects with familial type 1 diabetes

HUMAN MUTATION, Issue 4 2001
Issei Yoshiuchi
Abstract Mutations in the transcription factor hepatocyte nuclear factor-1, (HNF-1,; gene symbol TCF1) cause maturity-onset diabetes of the young type 3 (MODY3), a form of diabetes mellitus characterized by autosomal dominant inheritance, early onset, and pancreatic ,-cell dysfunction. Recent genetic studies, however, also found mutations in patients diagnosed with idiopathic (non-autoimmune based) type 1 diabetes. We identified a novel frameshift mutation (142delG) in the TCF1 gene in a family with a strong family history of type 1 diabetes and examined the functional properties of the mutant HNF 1,. The expression of the mutant protein was not detected in COS-7 cells by Western blot analysis after transfection of the mutant cDNA. This is the first case of an unstable mutant HNF-1, protein. Reporter gene analysis indicated that the mutant HNF-1, had no transactivation activity in HeLa and MIN6 cells. Haploinsufficiency for HNF-1, may lead to severe forms of diabetes like type 1 diabetes. Hum Mutat 18:345,351, 2001. © 2001 Wiley-Liss, Inc. [source]

Hereditary benign telangiectasia: first case in Iran

INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 7 2006
Zari Javidi
A 14-year-old boy was referred to the Dermatology Clinic of the Medical University of Mashhad, Iran, with numerous cutaneous telangiectasias on the face, ears, lips, and back of the hands, with lesions in the temporal region being the first to appear (Figs 1,3). His mother stated that the lesions had been present for 10 years with an increase in the past 6 months. He had no history of bleeding from the nose, mouth, gastrointestinal tract, and other mucosal surfaces, and there was no sign of organ involvement. On inspection, no lesions were detected on the nasal mucosa, external ear, over the tympanic membrane, or mouth. Figure 1. Numerous telangiectasias affecting the cheeks, nose, and perioral areas Figure 2. Lateral view of Fig. 1 Figure 3. Telangiectasias affecting the dorsal aspect of the hands The patient is one member of a family of six. His mother is healthy, but similar lesions were seen in his father, sister and one of his brothers with similar distributions. Lesions were also seen in his aunt and paternal grandmother, showing disease distribution in six members of this family from three generations. The oldest brother is 20 years of age and mentioned the onset of disease from the age of 10 years. The sister is 18 years of age and lesions started to appear 7 years ago; she claims that the lesions regress during her menstrual period. The youngest brother is 4 years of age and shows no sign of cutaneous lesions as yet. The parents are not consanguineous. Generalized telangiectasia with a predominant distribution on light-exposed skin, an autosomal dominant inheritance, and no sign of systemic or mucosal involvement and bleeding disorders indicates a diagnosis of hereditary benign telangiectasia. Our patient did not consent to biopsy. [source]

Oropharyngeal Skeletal Disease Accompanying High Bone Mass and Novel LRP5 Mutation,,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 5 2005
Michael R Rickels
Abstract Gain-of-function mutation in the gene encoding LRP5 causes high bone mass. A 59-year-old woman carrying a novel LRP5 missense mutation, Arg154Met, manifested skeletal disease affecting her oropharynx as well as dense bones, showing that exuberant LRP5 effects are not always benign. Introduction: Gain-of-function mutation (Gly171Val) of LDL receptor-related protein 5 (LRP5) was discovered in 2002 in two American kindreds with high bone mass and benign phenotypes. In 2003, however, skeletal disease was reported for individuals from the Americas and Europe carrying any of six novel LRP5 missense mutations affecting the same LRP5 protein domain. Furthermore, in 2004, we described a patient with neurologic complications from dense bones and extensive oropharyngeal exostoses caused by the Gly171Val defect. Materials and Methods: A 59-year-old woman was referred for dense bones. Three years before, mandibular buccal and lingual exostoses (osseous "tori") were removed because of infections from food trapping between the teeth and exostoses. Maxillary buccal and palatal exostoses were asymptomatic. Radiographic skeletal survey showed marked thickening of the skull base and diaphyses of long bones (endosteal hyperostosis). BMD Z scores assessed by DXA were +8.5 and +8.7 in the total hip and L1 -L4 spine (both ,195% average control), respectively. LRP5 mutation analysis was carried out for the LRP5 domain known to cause high bone mass. Results: Biochemical evaluation excluded most secondary causes of dense bones, and male-to-male transmission in her family indicated autosomal dominant inheritance. PCR amplification and sequencing of LRP5 exons 2-4 and adjacent splice sites revealed heterozygosity for a new LRP5 missense mutation, Arg154Met. Conclusions: LRP5 Arg154Met is a novel defect that changes the same first ",-propeller" module as the eight previously reported LRP5 gain-of-function missense mutations. Arg154Met alters a region important for LRP5 antagonism by dickkopf (Dkk). Therefore, our patient's extensive oropharyngeal exostoses and endosteal hyperostosis likely reflect increased Wnt signaling and show that exuberant LRP5 effects are not always benign. [source]

Gnathodiaphyseal Dysplasia: A Syndrome of Fibro-Osseous Lesions of Jawbones, Bone Fragility, and Long Bone Bowing

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2001
Mara Riminucci
Abstract We report an unusual generalized skeletal syndrome characterized by fibro-osseous lesions of the jawbones with a prominent psammomatoid body component, bone fragility, and bowing/sclerosis of tubular bones. The case fits with the emerging profile of a distinct syndrome with similarities to previously reported cases, some with an autosomal dominant inheritance and others sporadic. We suggest that the syndrome be named gnathodiaphyseal dysplasia. The patient had been diagnosed previously with polyostotic fibrous dysplasia (PFD) elsewhere, but further clinical evaluation, histopathological study, and mutation analysis excluded this diagnosis. In addition to providing a novel observation of an as yet poorly characterized syndrome, the case illustrates the need for stringent diagnostic criteria for FD. The jaw lesions showed fibro-osseous features with the histopathological characteristics of cemento-ossifying fibroma, psammomatoid variant. This case emphasizes that the boundaries between genuine GNAS1 mutation-positive FD and other fibro-osseous lesions occurring in the jawbones should be kept sharply defined, contrary to a prevailing tendency in the literature. A detailed pathological study revealed previously unreported features of cemento-ossifying fibroma, including the participation of myofibroblasts and the occurrence of psammomatoid bodies and aberrant mineralization, within the walls of blood vessels. Transplantation of stromal cells grown from the lesion into immunocompromised mice resulted in a close mimicry of the native lesion, including the sporadic formation of psammomatoid bodies, suggesting an intrinsic abnormality of bone-forming cells. [source]

A FAMILY WITH AUTOSOMAL DOMINANT MUTILATING NEUROPATHY NOT LINKED TO EITHER 3q13-q22 OR 9q22 LOCI

JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2000
E. Bellone
The clinical separation of CMT2 from HSAN I may be difficult in some kindreds in which the sensory and motor symptoms and deficits are approximately alike. The genetic studies of CMT2 families are also controversial: one form of CMT2 was shown to map on chromosome 3q13-q22 and named CMT2B; the HSAN I locus was mapped to 9q22.1. We describe a family with an autosomal dominant inheritance in which at least three members, belonging to three generations, developed a progressive neuropathy that combined limb weakness, wasting, and severe distal sensory loss leading to prominent mutilating changes. The onset was in late childhood, with progressive weakness in the lower limbs and later in the hands, resulting in a severe paralysis in the feet in one patient. Sensory disturbances were pronounced in 2 patients, and led to poorly healing ulcerations with osteomyelitis and amputations in one foot and mutilating lesions of both hands. Electrophysiological investigation revealed an axonopaty with consistent motor damage. Sural nerve biopsy showed a reduction in the density of both myelinated and unmyelinated fibers, with regenerating clusters. Linkage analysis using 5 microsatellite markers within to the critical 9q22 region was performed. Lod scores of this family calculated by LINKAGE package excluded association to this locus. We also performed linkage studies with chr. 3q13-q22 markers associated to the CMT2b locus. Lod scores excluded this locus as well as responsiblity of the familial phenotype. The severity of motor involvement would suggest classifying the disorder of this family as a form of HSMN II rather than HSAN, indicating that a new locus is involved in the pathogenesis of this disorder. [source]

Familial essential tremor with apparent autosomal dominant inheritance: Should we also consider other inheritance modes?

MOVEMENT DISORDERS, Issue 9 2006
Shaochun Ma MD
Abstract A positive family history is present in many patients with essential tremor (ET), but twin studies and segregation analysis have suggested that ET is not entirely a genetic disorder. Two genetic loci have been identified in autosomal dominant (AD) ET and polymorphisms in the DRD3 and HS1-BP3 genes have been proposed as the possible susceptibility factors for ET. There is also evidence for further genetic heterogeneity. We evaluated 4 unrelated large kindreds with ET with an apparent AD mode of transmission. Each kindred spanned at least 3 generations and contained at least 13 living affected subjects who met criteria for definitive ET. None of the pedigrees had evidence for inheritance of ET from both parents. Known genetic ET loci were excluded in these families. We detected a preferential transmission of ET in every kindred and the proportion of affected offspring varied from 75% to 90% (P < 0.05) in the generations with complete ascertainment. Our data indicate that non-Mendelian preferential transmission of an affected allele is a feature in many ET kindreds with multiple affected members and an apparent AD mode of inheritance. ET may have a complex etiology. Additional genetic models need to be considered, including an interaction of susceptibility genes and environmental risk factors. © 2006 Movement Disorder Society [source]

Familial cortical myoclonic tremor with epilepsy: A single syndromic classification for a group of pedigrees bearing common features

MOVEMENT DISORDERS, Issue 6 2005
Anne-Fleur Van Rootselaar MD
Abstract Fifty Japanese and European families with cortical myoclonic tremor and epilepsy have been reported under various names. Unfamiliarity with the syndrome often leads to an initial misdiagnosis of essential tremor or progressive myoclonus epilepsy. A detailed overview of the literature is lacking and is the scope of this study. Disease characteristics are adult onset, distal action tremor and myoclonus, epileptic seizures, autosomal dominant inheritance, benign course, effectiveness of antiepileptic drugs, and possibly cognitive decline. A channelopathy is hypothesized to be the basis of the disease. Despite phenotypic and genetic differences between the Japanese and European pedigrees, the clinical and electrophysiological data point toward one syndrome. To avoid confusion in literature and possible misdiagnosis of patients, we propose to use one description and suggest "familial cortical myoclonic tremor with epilepsy" (FCMTE). In addition, we put forward diagnostic criteria to give a starting point from which to conduct genetic studies. © 2005 Movement Disorder Society [source]

Autosomal Dominant Epidermodysplasia Verruciformis Lacking a Known EVER1 or EVER2 Mutation

PEDIATRIC DERMATOLOGY, Issue 3 2009
David F. McDermott M.D.
Epidermodysplasia verruciformis is a genetically heterogeneous disease, and autosomal recessive and X-linked inheritance patterns have been reported. Nonsense mutations in the genes EVER1 and EVER2 have been identified in over 75% of cases. We present epidermodysplasia verruciformis in a father and a son with typical histologic and clinical findings that occur in the absence of mutations in EVER1 or EVER2. Epidermodysplasia verruciformis in this father/son pair in a nonconsanguinous pedigree is consistent with autosomal dominant inheritance. This is the first report of autosomal dominant transmission of epidermodysplasia verruciformis, providing further evidence of the genetic heterogeneity of epidermodysplasia verruciformis. [source]

Genetics of atrioventricular conduction disease in humans

THE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 2 2004
D. Woodrow Benson
Abstract Atrioventricular (AV) conduction disease (block) describes impairment of the electrical continuity between the atria and ventricles. Classification of AV block has utilized biophysical characteristics, usually the extent (first, second, or third degree) and site of block (above or below His bundle recording site). The genetic significance of this classification is unknown. In young patients, AV block may result from injury or be the major cardiac manifestation of neuromuscular disease. However, in some cases, AV block has unknown or idiopathic cause. In such cases, familial clustering has been noted and published pedigrees show autosomal dominant inheritance; associated heart disease is common (e.g., congenital heart malformation, cardiomyopathy). The latter finding is not surprising given the common origin of working myocytes and specialized conduction system elements. Using genetic models incorporating reduced penetrance (disease absence in some individuals with disease gene), variable expressivity (individuals with disease gene have different phenotypes), and genetic heterogeneity (similar phenotypes, different genetic cause), molecular genetic causes of AV block are being identified. Mutations identified in genes with diverse functions (transcription, excitability, and energy homeostasis) for the first time provide the means to assess risk and offer insight into the molecular basis of this important clinical condition previously defined only by biophysical characteristics. © 2004 Wiley-Liss, Inc. [source]

Analysis of family history of palmoplantar hyperhidrosis in Japan

THE JOURNAL OF DERMATOLOGY, Issue 12 2009
Noriko YAMASHITA
Abstract Palmoplantar hyperhidrosis (PPH) is a disorder characterized by excessive sweating of the palmar surfaces of the hands and feet due to emotional sweating. There have been reports based on family histories, and the involvement of genetic factors has been suggested. Among 410 PPH patients who visited our hospital from August 2006 to October 2008, onset age and family history were investigated in order to prepare pedigree charts, and family histories were confirmed in 147 patients (36%). Between the family history and negative family history (sporadic) groups, no significant differences were seen in onset age, sex or sweat volume. With regard to the patterns of incidence within families, parent,child was the most common at 58%, followed by sibling cases at 18%. The incidence of PPH in three generations was 13%. Pedigree charts prepared based on data obtained by patient interviews suggested autosomal dominant inheritance. [source]

Six novel mutations of the ADAR1 gene in patients with dyschromatosis symmetrica hereditaria: Histological observation and comparison of genotypes and clinical phenotypes

THE JOURNAL OF DERMATOLOGY, Issue 7 2008
Taisuke KONDO
ABSTRACT Dyschromatosis symmetrica hereditaria (DSH), is a pigmentary genodermatosis of autosomal dominant inheritance. Since we clarified that the disease is caused by a mutation of the adenosine deaminase acting on the RNA 1 gene (ADAR1) in 2003, the molecular pathogenesis of a peculiar clinical feature of the disease has been expected to be clarified. We examined five familial cases and one sporadic case of Japanese families with DSH. The mutation analyses were done with single-strand conformation polymorphism/heteroduplex (SSCP/HD) analysis and direct sequencing of ADAR1. The DNA analysis of each patient revealed one missense mutation (p.F1091S), two nonsense mutations (p.C893X, p.S581X) and three frame-shift mutations (p.E498fsX517, p.F1091fsX1092, p.L855fsX856). Visual and electron microscopic findings showed abundant melanin pigment deposited all over the basal layer, and enlarged melanocytes with long dendrites located in the pigmented lesions with small or immature melanosomes scattered sparsely in the cytoplasm, but in the adjacent keratinocytes many small melanosomes were singly dispersed or aggregated. The hypopigmented areas showed little melanin deposition and reduced numbers of melanocytes in which much degenerative cytoplasmic vacuole formation could be observed by electron microscopy. Herein, we report six cases of DSH with six novel mutations. The variety of their clinical phenotypes even in the pedigree may suggest the presence of factors other than the ADAR1 gene influencing the extent of the clinical skin lesion. Microscopic findings suggest that the clinical appearance must have developed directly by melanocyte variations mainly induced by the ADAR1 gene mutations. [source]

Genetic mapping of the belt pattern in Brown Swiss cattle to BTA3

ANIMAL GENETICS, Issue 2 2009
C. Drögemüller
Summary The white belt pattern of Brown Swiss cattle is characterized by a lack of melanocytes in a stretch of skin around the midsection. This pattern is of variable width and sometimes the belt does not fully circle the body. To identify the gene responsible for this colour variation, we performed linkage mapping of the belted locus using six segregating half-sib families including 104 informative meioses for the belted character. The pedigree confirmed a monogenic autosomal dominant inheritance of the belted phenotype in Brown Swiss cattle. We performed a genome scan using 186 microsatellite markers in a subset of 88 animals of the six families. Linkage with the belt phenotype was detected at the telomeric region of BTA3. Fine-mapping and haplotype analysis using 19 additional markers in this region refined the critical region of the belted locus to a 922-kb interval on BTA3. As the corresponding human and mouse chromosome segments contain no obvious candidate gene for this coat colour trait, the mutation causing the belt pattern in the Brown Swiss cattle might help to identify an unknown gene influencing skin pigmentation. [source]

Familial atrophia maculosa varioliformis cutis: case report and pedigree analysis

BRITISH JOURNAL OF DERMATOLOGY, Issue 4 2005
T. Qu
Summary Atrophia maculosa varioliformis cutis (AVMC) was first described in 1918, as a rarely reported form of idiopathic macular atrophy on the cheeks. Nineteen patients have been reported in the past 86 years. Recently we diagnosed a 25-year-old woman as AMVC and investigated her family history. We collected the clinical data of the pedigree and presumed that AVMV is in a autosomal dominant inheritance. [source]

Epidemiology, clinical presentation and diagnosis of onychomycosis

BRITISH JOURNAL OF DERMATOLOGY, Issue 2003
J. Faergemann
Summary Onychomycosis is a common nail disease, responsible for up to 50% of diseases of the nail. The distribution of different pathogens is not uniform; it depends on various factors such as climate, geography and migration. However, studies have revealed that two dermatophytes, Trichophyton rubrum and Trichophyton mentagrophytes, account for more than 90% of onychomycoses. Onychomycosis can be divided into four major clinical presentations: distal subungal (the most common form of the disease), proximal subungal (the most common form found in patients with human immunodeficiency virus infection), and superficial and total dystrophic onychomycosis. Onychomycosis is a multifactorial disease. Age has a very important effect on the occurrence of onychomycosis, with a correlation between increasing age and infection. Genetics has also been identified as a factor governing the epidemiology of onychomycosis; T. rubrum infection shows a familial pattern of autosomal dominant inheritance. Disease and lifestyle may also play a role in the epidemiology of fungal nail infections. Studies have shown that diabetes, acquired immunodeficiency syndrome and peripheral arterial disease may be independent predictors of onychomycosis. Because of the multifactorial nature of the epidemiology, accurate diagnosis, pertinent treatment and patient education must be paramount when treating the disease. [source]

Familial vasopressin-sensitive ACTH-independent macronodular adrenal hyperplasia (VPs-AIMAH): clinical studies of three kindreds

CLINICAL ENDOCRINOLOGY, Issue 6 2009
Lucia Gagliardi
Summary Objective, Cushing's syndrome due to familial ACTH-independent macronodular adrenal hyperplasia (AIMAH) has been reported in small kindreds. In vasopressin-sensitive AIMAH (VPs-AIMAH), VP stimulates an aberrant, ACTH-independent increase in cortisol. The aims of this study were to (i) delineate the preclinical phenotype of VPs-AIMAH in a three-generation kindred (AIMAH-01) and two smaller kindreds (AIMAH-02 and AIMAH-03) and (ii) investigate the aetiology of VP sensitivity in AIMAH-01. Design, Clinical studies of three kindreds for adrenal tumours or early Cushing's and molecular studies of adrenal tumours (AIMAH-01). Patients, Thirty-three individuals, from three kindreds, were screened for perturbations of the hypothalamic,pituitary,adrenal axis or adrenal tumours. Measurements, Patients underwent clinical, biochemical and adrenal imaging investigations. Evaluation included low-dose (1 IU/70 kg) VP stimulation. Adrenal VP receptor (AVPR1A, AVPR1B, AVPR2) expression (AIMAH-01) was assessed using RT-PCR and immunohistochemistry (IHC). IHC for VP was also performed. Results, AIMAH-01 had three siblings with Cushing's, and four individuals with suppressed ACTH/aberrant VP responses and/or adrenal nodules. In AIMAH-02, a father and son were affected. AIMAH-03 had three siblings with Cushing's. RT-PCR showed adrenal overexpression of AVPR1A and AVPR1B. IHC detected AVPR1A. The adrenal tumour from one patient also stained weakly for VP and AVPR2. Conclusion, Adrenal nodules, suppressed ACTH and increased VP sensitivity may represent preclinical disease, allowing early detection, and treatment, of affected individuals. In AIMAH-01, increased VP sensitivity may be due to adrenal VP receptor overexpression. In these kindreds, VPs-AIMAH is familial, and autosomal dominant inheritance is most likely. [source]