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“Homozygous, and compound heterozygous mutation in 3 Turkish family with Jervell and Lange-Nielsen syndrome: case reports”

BACKGROUND: Jervell 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, addi...

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Autores principales: Uysal, Fahrettin, Turkgenc, Burcu, Toksoy, Guven, Bostan, Ozlem M., Evke, Elif, Uyguner, Oya, Yakicier, Cengiz, Kayserili, Hulya, Cil, Ergun, Temel, Sehime G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5644177/
https://www.ncbi.nlm.nih.gov/pubmed/29037160
http://dx.doi.org/10.1186/s12881-017-0474-8
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author Uysal, Fahrettin
Turkgenc, Burcu
Toksoy, Guven
Bostan, Ozlem M.
Evke, Elif
Uyguner, Oya
Yakicier, Cengiz
Kayserili, Hulya
Cil, Ergun
Temel, Sehime G.
author_facet Uysal, Fahrettin
Turkgenc, Burcu
Toksoy, Guven
Bostan, Ozlem M.
Evke, Elif
Uyguner, Oya
Yakicier, Cengiz
Kayserili, Hulya
Cil, Ergun
Temel, Sehime G.
author_sort Uysal, Fahrettin
collection PubMed
description BACKGROUND: Jervell 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 PRESENTATIONS: Three 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. CONCLUSIONS: Three 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.
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spelling pubmed-56441772017-10-26 “Homozygous, and compound heterozygous mutation in 3 Turkish family with Jervell and Lange-Nielsen syndrome: case reports” Uysal, Fahrettin Turkgenc, Burcu Toksoy, Guven Bostan, Ozlem M. Evke, Elif Uyguner, Oya Yakicier, Cengiz Kayserili, Hulya Cil, Ergun Temel, Sehime G. BMC Med Genet Case Report BACKGROUND: Jervell 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 PRESENTATIONS: Three 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. CONCLUSIONS: Three 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. BioMed Central 2017-10-16 /pmc/articles/PMC5644177/ /pubmed/29037160 http://dx.doi.org/10.1186/s12881-017-0474-8 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Case Report
Uysal, Fahrettin
Turkgenc, Burcu
Toksoy, Guven
Bostan, Ozlem M.
Evke, Elif
Uyguner, Oya
Yakicier, Cengiz
Kayserili, Hulya
Cil, Ergun
Temel, Sehime G.
“Homozygous, and compound heterozygous mutation in 3 Turkish family with Jervell and Lange-Nielsen syndrome: case reports”
title “Homozygous, and compound heterozygous mutation in 3 Turkish family with Jervell and Lange-Nielsen syndrome: case reports”
title_full “Homozygous, and compound heterozygous mutation in 3 Turkish family with Jervell and Lange-Nielsen syndrome: case reports”
title_fullStr “Homozygous, and compound heterozygous mutation in 3 Turkish family with Jervell and Lange-Nielsen syndrome: case reports”
title_full_unstemmed “Homozygous, and compound heterozygous mutation in 3 Turkish family with Jervell and Lange-Nielsen syndrome: case reports”
title_short “Homozygous, and compound heterozygous mutation in 3 Turkish family with Jervell and Lange-Nielsen syndrome: case reports”
title_sort “homozygous, and compound heterozygous mutation in 3 turkish family with jervell and lange-nielsen syndrome: case reports”
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5644177/
https://www.ncbi.nlm.nih.gov/pubmed/29037160
http://dx.doi.org/10.1186/s12881-017-0474-8
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