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Variants in the genes DCTN2,DNAH10,LRIG3, and MYO1A are associated with intermediate Charcot–Marie–Tooth disease in a Norwegian family

INTRODUCTION: Charcot–Marie–Tooth disease (CMT) is a heterogeneous inherited neuropathy. The number of known CMT genes is rapidly increasing mainly due to next‐generation sequencing technology, at present more than 70 CMT‐associated genes are known. We investigated whether variants in the DCTN2 coul...

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Autores principales: Braathen, G. J., Høyer, H., Busk, Ø. L., Tveten, K., Skjelbred, C. F., Russell, M. B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5057358/
https://www.ncbi.nlm.nih.gov/pubmed/26517670
http://dx.doi.org/10.1111/ane.12515
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author Braathen, G. J.
Høyer, H.
Busk, Ø. L.
Tveten, K.
Skjelbred, C. F.
Russell, M. B.
author_facet Braathen, G. J.
Høyer, H.
Busk, Ø. L.
Tveten, K.
Skjelbred, C. F.
Russell, M. B.
author_sort Braathen, G. J.
collection PubMed
description INTRODUCTION: Charcot–Marie–Tooth disease (CMT) is a heterogeneous inherited neuropathy. The number of known CMT genes is rapidly increasing mainly due to next‐generation sequencing technology, at present more than 70 CMT‐associated genes are known. We investigated whether variants in the DCTN2 could cause CMT. MATERIAL AND METHODS: Fifty‐nine Norwegian CMT families from the general population with unknown genotype were tested by targeted next‐generation sequencing (NGS) for variants in DCTN2 along with 32 CMT genes and 19 other genes causing other inherited neuropathies or neuronopathies, due to phenotypic overlap. In the family with the DCTN2 variant, exome sequencing was then carried out on all available eight family members to rule out the presence of more potential variants. RESULTS: Targeted NGS identified in one family a variant of DCTN2, c.337C>T, segregating with the phenotype in five affected members, while it was not present in the three unaffected members. The DCTN2 variant c.337C>T; p.(His113Tyr) was neither found in in‐house controls nor in SNP databases. Exome sequencing revealed a singular heterozygous shared haplotype containing four genes, DCTN2,DNAH10,LRIG3, and MYO1A, with novel sequence variants. The haplotype was shared by all the affected members, while the unaffected members did not have it. CONCLUSIONS: This is the first time a haplotype on chromosome 12 containing sequence variants in the genes DCTN2,DNAH10,LRIG3, and MYO1A has been linked to an inherited neuropathy in humans.
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spelling pubmed-50573582016-10-19 Variants in the genes DCTN2,DNAH10,LRIG3, and MYO1A are associated with intermediate Charcot–Marie–Tooth disease in a Norwegian family Braathen, G. J. Høyer, H. Busk, Ø. L. Tveten, K. Skjelbred, C. F. Russell, M. B. Acta Neurol Scand Original Articles INTRODUCTION: Charcot–Marie–Tooth disease (CMT) is a heterogeneous inherited neuropathy. The number of known CMT genes is rapidly increasing mainly due to next‐generation sequencing technology, at present more than 70 CMT‐associated genes are known. We investigated whether variants in the DCTN2 could cause CMT. MATERIAL AND METHODS: Fifty‐nine Norwegian CMT families from the general population with unknown genotype were tested by targeted next‐generation sequencing (NGS) for variants in DCTN2 along with 32 CMT genes and 19 other genes causing other inherited neuropathies or neuronopathies, due to phenotypic overlap. In the family with the DCTN2 variant, exome sequencing was then carried out on all available eight family members to rule out the presence of more potential variants. RESULTS: Targeted NGS identified in one family a variant of DCTN2, c.337C>T, segregating with the phenotype in five affected members, while it was not present in the three unaffected members. The DCTN2 variant c.337C>T; p.(His113Tyr) was neither found in in‐house controls nor in SNP databases. Exome sequencing revealed a singular heterozygous shared haplotype containing four genes, DCTN2,DNAH10,LRIG3, and MYO1A, with novel sequence variants. The haplotype was shared by all the affected members, while the unaffected members did not have it. CONCLUSIONS: This is the first time a haplotype on chromosome 12 containing sequence variants in the genes DCTN2,DNAH10,LRIG3, and MYO1A has been linked to an inherited neuropathy in humans. John Wiley and Sons Inc. 2015-10-12 2016-07 /pmc/articles/PMC5057358/ /pubmed/26517670 http://dx.doi.org/10.1111/ane.12515 Text en © 2015 The Authors. Acta Neurologica Scandinavica Published by John Wiley & Sons Ltd This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Braathen, G. J.
Høyer, H.
Busk, Ø. L.
Tveten, K.
Skjelbred, C. F.
Russell, M. B.
Variants in the genes DCTN2,DNAH10,LRIG3, and MYO1A are associated with intermediate Charcot–Marie–Tooth disease in a Norwegian family
title Variants in the genes DCTN2,DNAH10,LRIG3, and MYO1A are associated with intermediate Charcot–Marie–Tooth disease in a Norwegian family
title_full Variants in the genes DCTN2,DNAH10,LRIG3, and MYO1A are associated with intermediate Charcot–Marie–Tooth disease in a Norwegian family
title_fullStr Variants in the genes DCTN2,DNAH10,LRIG3, and MYO1A are associated with intermediate Charcot–Marie–Tooth disease in a Norwegian family
title_full_unstemmed Variants in the genes DCTN2,DNAH10,LRIG3, and MYO1A are associated with intermediate Charcot–Marie–Tooth disease in a Norwegian family
title_short Variants in the genes DCTN2,DNAH10,LRIG3, and MYO1A are associated with intermediate Charcot–Marie–Tooth disease in a Norwegian family
title_sort variants in the genes dctn2,dnah10,lrig3, and myo1a are associated with intermediate charcot–marie–tooth disease in a norwegian family
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5057358/
https://www.ncbi.nlm.nih.gov/pubmed/26517670
http://dx.doi.org/10.1111/ane.12515
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