Search results for "Pedigree"
showing 10 items of 313 documents
Familial seborrhoeic keratosis associated with multiple 'pure reticulated acanthomas' and infundibulocystic basal cell carcinomas.
2017
Background A variety of genodermatoses with multiple cutaneous tumors with germline genetic alterations such as Gorlin syndrome with PTCH1 gene mutations have been described. Other cutaneous syndromes have been associated with somatic gene mutations, such as FGFR3 in familial seborrhoeic keratosis. Objective We describe the clinical, dermoscopic, and histopathological features of multiple cutaneous lesions, mostly infundibulocystic basal cell carcinomas and pure reticulated acanthomas, present in a family affected by familial seborrhoeic keratosis. In addition, we tested for possible germline alterations in the FGFR3 and PTCH1 genes. Methods Ten members of one family were clinically examine…
A c.1244G>A (p.Arg415Gln) mutation in SH3BP2 gene causes cherubism in a Turkish family: report of a family with review of the literature
2014
Objectives: The present study was aimed at advancing the understanding of the pathogenesis of cherubism by presenting a case study based on history, physical examination, typical radiological features, molecular and histo - pathological laboratory tests and a review of the literature. Study Design: This study began with a 7-year-old boy who was referred due to mandibular overgrowth. A pan - oramic radiograph revealed multilocular radiolucent lesions of the upper/lower jaws suggestive of cherubism. Overall, a total of four family members were tested for SH3BP2 mutations, namely two siblings and their parents. Both siblings had been clinically diagnosed with cherubism; however, the parents we…
Familial thoracic aortic aneurysm/dissection with patent ductus arteriosus: genetic arguments for a particular pathophysiological entity.
2004
International audience; Thoracic aortic aneurysm and aortic dissection (TAA and AD) are an important cause of sudden death. Familial cases could account for 20% of all cases. A genetic heterogeneity with two identified genes (FBN1 and COL3A1) and three loci (3p24-25 or MFS2/TAAD2, 5q13-q14 and 11q23.2-24) has been shown previously. Study of a single family composed of 179 members with an abnormally high occurrence of TAA/AD disease. A total of 40 subjects from three generations were investigated. In addition to five cases of stroke and three cases of sudden death, there were four cases of AD and four cases of TAA in adults. In all, 11 cases of patent ductus arteriosus (PDA) were observed, t…
Complement component deficiencies and infection: C5, C8 and C3 deficiencies in three families.
1992
Three families are described with complement component deficiencies. In one family, five children had C5 deficiency; in a second family, two children had C8 deficiency and one child in a third family had C3 deficiency. The index cases were identified during screening of patients with recurrent pyogenic infections, recurrent meningitis and meningococcaemia. Two of the five C5 deficient patients had recurrent meningitis and meningococcaemia, two had recurrent respiratory tract infections and otitis and one was healthy. One of the C8 deficient patients had meningitis, meningococcaemia and pneumonia, whereas his sibling with the same deficiency was healthy. The patient with C3 deficiency had fo…
A second family with familial AD and the V717L APP mutation has a later age at onset
2006
Four mutations have been reported at the 717 codon of the amyloid precursor protein (APP), with valine substituted by isoleucine, glycine, phenylalanine, and leucine. While several families with the isoleucine substitution have been described, the other substitutions have been reported in only one family each worldwide. A family with the V717L APP mutation has been previously reported,1 with a mean age at onset of 38 years (range 35 to 39), based on four affected family members, and a mean age at death of 46 years (range 40 to 50). We have identified a second family with a later mean age at onset of 50 years (range 48 to 57) and mean age at death of 61 years (range 57 to 68). Family 171 is …
A methodological strategy for PAH genotyping in populations with a marked molecular heterogeneity of hyperphenylalaninemia.
2001
Abstract The elucidation of the molecular basis of hyperphenylalaninemia in various world populations (PKU Consortium Database: http://www.mcgill.ca/pahdb/) has revealed a remarkable molecular heterogeneity at the locus encoding for phenylalanine hydroxylase. As a consequence, genotyping of HPA patients has prompted the establishment of an impressive number of mutation detection protocols. In spite of the large variety of methods proposed so far, no comprehensive strategy has been yet developed for the detection of PAH gene mutations. Therefore, new approaches, combining the advantages of individual methods are required, especially in populations with a high number of PAH gene mutations. In…
Targeted next-generation sequencing of deafness genes in hearing-impaired individuals uncovers informative mutations
2014
Purpose: Targeted next-generation sequencing provides a remarkable opportunity to identify variants in known disease genes, particularly in extremely heterogeneous disorders such as nonsyndromic hearing loss. The present study attempts to shed light on the complexity of hearing impairment. Methods: Using one of two next-generation sequencing panels containing either 80 or 129 deafness genes, we screened 30 individuals with nonsyndromic hearing loss (from 23 unrelated families) and analyzed 9 normal-hearing controls. Results: Overall, we found an average of 3.7 variants (in 80 genes) with deleterious prediction outcome, including a number of novel variants, in individuals with nonsyndromic h…
Mutation ofPOC1Bin a Severe Syndromic Retinal Ciliopathy
2014
We describe a consanguineous Iraqi family with Leber congenital amaurosis (LCA), Joubert syndrome (JBTS), and polycystic kidney disease (PKD). Targeted next-generation sequencing for excluding mutations in known LCA and JBTS genes, homozygosity mapping, and whole-exome sequencing identified a homozygous missense variant, c.317G>C (p.Arg106Pro), in POC1B, a gene essential for ciliogenesis, basal body, and centrosome integrity. In silico modeling suggested a requirement of p.Arg106 for the formation of the third WD40 repeat and a protein interaction interface. In human and mouse retina, POC1B localized to the basal body and centriole adjacent to the connecting cilium of photoreceptors and in …
Concordance of assays designed for the quantification of JAK2V617F: a multicenter study
2008
Background Many different techniques have been designed for the quantification of JAK2 V617F allelic burden, sometimes producing discrepant results. Design and Methods JAK2 V617F quantification techniques were compared among 16 centers using 11 assays based on quantitative polymerase chain reaction (with mutation-specific primers or probes, or fluorescent resonance energy transfer/melting curve analysis), allele-specific polymerase chain reaction, conventional sequencing or pyrosequencing. Results A first series of blinded samples (granulocyte DNA, n=29) was analyzed. Seven assays (12 centers) reported values inside the mean±2SD; the mean coefficient of variation was 31%. Sequencing techniq…
The c.43_44insCTG variation in PCSK9 is associated with low plasma LDL-cholesterol in a Caucasian population.
2006
Abstract The genetic etiology of familial hypobetalipoproteinemia (FHBL) is unclear in the majority of cases. Mutations in apolipoprotein B (APOB) are the only confirmed causes of FHBL. Recently, loss-of-function mutations of PCSK9 gene have been shown to be associated with the hypocholesterolemia phenotype. Our primary goal was to confirm that mutations in PCSK9 could be another cause of FHBL. Using the sequencing approach, we found that the c.43_44insCTG variation in PCSK9, a common in-frame insertion in both African American and Caucasian populations, is associated with the hypocholesterolemia phenotype in three FHBL families. Then we tested whether this variation could be associated wit…