Search results for "Pedigree"
showing 10 items of 313 documents
A dominant gene for developmental dyslexia on chromosome 3.
2001
Developmental dyslexia is a neurofunctional disorder characterised by an unexpected difficulty in learning to read and write despite adequate intelligence, motivation, and education. Previous studies have suggested mostly quantitative susceptibility loci for dyslexia on chromosomes 1, 2, 6, and 15, but no genes have been identified yet. We studied a large pedigree, ascertained from 140 families considered, segregating pronounced dyslexia in an autosomal dominant fashion. Affected status and the subtype of dyslexia were determined by neuropsychological tests. A genome scan with 320 markers showed a novel dominant locus linked to dyslexia in the pericentromeric region of chromosome 3 with a m…
Familial dyslexia: neurocognitive and genetic correlation in a large Finnish family.
2007
Neuropsychological findings of individuals with dyslexia (n=24) from a large, three-generation Finnish family are presented. We have previously performed whole genome linkage scanning in this family and found that dyslexia in this kindred segregates with a single locus in the pericentromeric area of chromosome 3. Those included in the analyses were carefully evaluated for general cognitive ability, reading and spelling skills, and reading-related neurocognitive skills. The neurocognitive type of dyslexia segregating in this family consisted of deficits in phonological awareness, verbal short-term memory, and rapid naming. Severe dyslexia also seemed to be connected with a general language d…
GAA trinucleotide repeat expansion in variant Friedreich's ataxia families.
1997
Phenotypic variants in Friedreich's ataxia include late onset, preservation of the lower limbs tendon reflexes, and slow progression. We describe clinical and electrophysiological features from three families with Friedreichlike phenotypes. Friedreich's ataxia diagnosis was confirmed by finding two allelic expansions of the GAA trinucleotide repeat at the X25 gene. In family 1 both patients had a late-onset phenotype with preservation of knee and ankle jerks, lack of cardiomyopathy, and preserved H reflex. One of them did not have electrophysiologic evidence of sensory axonal neuropathy. Patients from family 2 showed variability in the age of onset, and 2 out of 3 affected children had hype…
Mutations in ARL2BP, Encoding ADP-Ribosylation-Factor-Like 2 Binding Protein, Cause Autosomal-Recessive Retinitis Pigmentosa
2013
Retinitis pigmentosa (RP) is a genetically heterogeneous retinal degeneration characterized by photoreceptor death, which results in visual failure. Here, we used a combination of homozygosity mapping and exome sequencing to identify mutations in ARL2BP, which encodes an effector protein of the small GTPases ARL2 and ARL3, as causative for autosomal-recessive RP (RP66). In a family affected by RP and situs inversus, a homozygous, splice-acceptor mutation, c.101−1G>C, which alters pre-mRNA splicing of ARLBP2 in blood RNA, was identified. In another family, a homozygous c.134T>G (p.Met45Arg) mutation was identified. In the mouse retina, ARL2BP localized to the basal body and cilium-associated…
Gly114Asp mutation of rhodopsin in autosomal dominant retinitis pigmentosa
1995
Two autosomal dominant retinitis pigmentosa families of different origin were screened for rhodopsin mutations using the method of single strand conformation polymorphism and direct sequencing. We found a CGG-CAG substitution in codon 114 of rhodopsin in both families. This change predicted the replacement of a glycine by an aspartic acid and suggested that this change is the cause of the disease in these families.
Autosomal-recessive SASH1 variants associated with a new genodermatosis with pigmentation defects, palmoplantar keratoderma and skin carcinoma
2014
SASH1 (SAM and SH3 domain-containing protein 1) is a tumor suppressor gene involved in the tumorigenesis of a spectrum of solid cancers. Heterozygous SASH1 variants are known to cause autosomal-dominant dyschromatosis. Homozygosity mapping and whole-exome sequencing were performed in a consanguineous Moroccan family with two affected siblings presenting an unclassified phenotype associating an abnormal pigmentation pattern (hypo- and hyperpigmented macules of the trunk and face and areas of reticular hypo- and hyperpigmentation of the extremities), alopecia, palmoplantar keratoderma, ungueal dystrophy and recurrent spinocellular carcinoma. We identified a homozygous variant in SASH1 (c.1849…
Phenotypic variability in patients with generalised resistance to thyroid hormone.
1995
Genetic linkage of generalised resistance to thyroid hormone (GRTH) to the human thyroid receptor beta 1 gene has been identified. To date 38 different mutations in several kindreds have been documented. We report on a family with GRTH displaying an adenine for guanine substitution at nucleotide 1234 resulting in a threonine for alanine substitution at codon 317 of exon 9. This mutation has been described for different phenotypes, suggesting that the heterogeneity in GRTH may be the result of multiple genetic factors.
A novel constitutional mutation affecting splicing of retinoblastoma tumor suppressor gene intron 23 causes partial loss of pRB activity.
2005
Hereditary predisposition to retinoblastoma is caused by germ line mutations in the RB1 gene. Genetic counseling of affected individuals and accurate risk prediction for their families requires identification of the disease causing mutation. Furthermore, the nature of a mutation can determine genetic penetrance, disease presentation and prognosis. We describe, and functionally characterize here, a novel mutant allele of RB1 present in the germ line of a patient with sporadic bilateral retinoblastoma. The mutation generates an operational splice acceptor site resulting in a predicted protein product with loss of 81 amino acids from its carboxy terminus. We demonstrate that the aberrantly spl…
Clinical features and molecular genetic analysis in a Turkish family with oral white sponge nevus
2018
Background Oral white sponge nevus (WSN) is a rare autosomal dominant benign condition, characterized by asymptomatic spongy white plaques. Mutations in Keratin 4 (KRT4) and 13 (KRT13) have been shown to cause WSN. Familial cases are uncommon due to irregular penetrance. Thus, the aim of the study was: a) to demonstrate the clinical and histopathological features of a three-generation Turkish family with oral WSN b) to determine whether KRT4 or KRT13 gene mutation was the molecular basis of WSN. Material and Methods Out of twenty members of the family ten were available for assessment. Venous blood samples from six affected and five unaffected members and 48 healthy controls were obtained f…
Clinical, histological and genetic characterization of reducing body myopathy caused by mutations in FHL1
2008
We recently identified the X-chromosomal four and a half LIM domain gene FHL1 as the causative gene for reducing body myopathy, a disorder characterized by progressive weakness and intracytoplasmic aggregates in muscle that exert reducing activity on menadione nitro-blue-tetrazolium (NBT). The mutations detected in FHL1 affected highly conserved zinc coordinating residues within the second LIM domain and lead to the formation of aggregates when transfected into cells. Our aim was to define the clinical and morphological phenotype of this myopathy and to assess the mutational spectrum of FHL1 mutations in reducing body myopathy in a larger cohort of patients. Patients were ascertained via th…