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Autozygosity in a Turkish family with scoliosis, blindness, and arachnodactyly syndrome.

ABSTRACT: Blindness-scoliosis-arachnodactyly syndrome has been described in a family with parental consanguinity. We present the strategy employed to determine the gene locus responsible for the syndrome.A retrospective study of blindness-scoliosis-arachnodactyly syndrome patients at the Department of Medical Genetics, Erciyes University, between 2009-2010.Whole genome single nucleotide polymorphisms (SNPs) were scanned using a 250K Affymetrix array. We visually evaluated runs of homozygosity shared by two affected brothers that segregated in the entire pedigree with different combinations due to the unclear affected status of some siblings. Two and multiple-point LOD (logarithm [base 10] of odds) score analyses were performed by easyLINKAGEplus v5.08.Five homozygous blocks over 2 Mb shared by two affected brothers segregated with phenotype in two affected and three unaffected siblings and in the mother whose phenotypes were unequivocal. The longest homozygous block in this analysis was on chromosome 14 between 67817621bp (rs7148416) and 82508151bp (rs17117757). When another sister with positive eye findings was added to the analysis, this region was narrowed to between 67817621bp (rs7148416) and 75657598bp (rs11626830), with a maximum LOD score of 2.3956 by two-point analysis. Three candidate genes were detected in this region.This study contributes to the existing literature on the region 67817621 bp 82508151 bp (rs17117757) on chromosome 14 and the three candidate genes, which could be responsible for the syndrome.

SUBMITTER: Orenay-Boyacioglu S

PROVIDER: S-EPMC6074473 | biostudies-literature | 2015 Nov-Dec

REPOSITORIES: biostudies-literature

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Autozygosity in a Turkish family with scoliosis, blindness, and arachnodactyly syndrome.

Orenay-Boyacioglu Seda S Tekin Mustafa M Dundar Munis M

Annals of Saudi medicine 20151101 6

<h4>Background and objectives</h4>Blindness-scoliosis-arachnodactyly syndrome has been described in a family with parental consanguinity. We present the strategy employed to determine the gene locus responsible for the syndrome.<h4>Design and setting</h4>A retrospective study of blindness-scoliosis-arachnodactyly syndrome patients at the Department of Medical Genetics, Erciyes University, between 2009-2010.<h4>Patients and methods</h4>Whole genome single nucleotide polymorphisms (SNPs) were scan ...[more]

PMID: 26657231

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Project description:BackgroundJervell and Lange-Nielsen syndrome (JLNS) isa recessive model of long QT syndrome which might also be related to possible hearing loss. Although the syndrome has been demonstrated to be originated from homozygous or compound heterozygous mutations in either the KCNQ1 or KCNE1 genes, additional mutations in other genetic loci should be considered, particularly in malignant course patients.Case presentationsThree patients were admitted into hospital due to recurrent seizures/syncope, intrauterine and postnatal bradycardia respectively; moreover all three patients had congenital sensorineural hearing-loss. Their electrocardiograms showed markedly prolonged QT interval. Implantable defibrillator was implanted and left cardiac sympathetic denervation was performed due to the progressive disease in case 1. She had countless ventricular fibrillation and appropriate shock while using an implantable defibrillator. The DNA sequencing analysis of the KCNQ1 gene disclosed a homozygous c.728G > A (p.Arg243His) missense mutation in case1. Further targeted next generation sequencing of cardiac panel comprising 68 gene revealed a heterozygous c.1346 T > G (p.Ile449Arg) variant in RYR2 gene and a heterozygous c.809G > A (p.Cys270Tyr) variant in NKX2-5 gene in the same patient. Additional gene alterations in RYR2 and NKX2-5 genes were thought to be responsible for progressive and malignant course of the disease. As a result of DNA sequencing analysis of KCNQ1 and KCNE1 genes, a compound heterozygosity for two mutations had been detected in KCNQ1 gene in case 2: a maternally derived c.477 + 1G > A splice site mutation and a paternally derived c.520C > T (p.Arg174Cys) missense mutation. Sanger sequencing of KCNQ1 and KCNE1 genes displayed a homozygous c.1097G > A (p.Arg366Gln) mutation in KCNQ1 gene in case 3. β-blocker therapy was initiated to all the index subjects.ConclusionsThree families of JLNS who presented with long QT and deafness and who carry homozygous, or compound heterozygous mutation in KCNQ1 gene were presented in this report. It was emphasized that broad targeted cardiac panels may be useful to predict the outcome especially in patients with unexplained phenotype-genotype correlation. Clinical presentations and molecular findings will be discussed further to clarify the phenotype genotype associations.

Dataset Information

Autozygosity in a Turkish family with scoliosis, blindness, and arachnodactyly syndrome.

Publications

Autozygosity in a Turkish family with scoliosis, blindness, and arachnodactyly syndrome.

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