Whole Exome Sequencing as a Diagnostic Tool for Unidentified Muscular Dystrophy in a Vietnamese Family
Muscular dystrophies are a group of heterogeneous clinical and genetic disorders. Two siblings presented with characteristics like muscular dystrophy, abnormal white matter, and elevated serum creatine kinase level. The high throughput of whole exome sequencing (WES) makes it an efficient tool for o...
Main Authors: | , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2020-09-01
|
Series: | Diagnostics |
Subjects: | |
Online Access: | https://www.mdpi.com/2075-4418/10/10/741 |
id |
doaj-74a9c9b3fc854d2ab0b7a4e4d111c942 |
---|---|
record_format |
Article |
spelling |
doaj-74a9c9b3fc854d2ab0b7a4e4d111c9422020-11-25T03:14:02ZengMDPI AGDiagnostics2075-44182020-09-011074174110.3390/diagnostics10100741Whole Exome Sequencing as a Diagnostic Tool for Unidentified Muscular Dystrophy in a Vietnamese FamilyNgoc-Lan Nguyen0Can Thi Bich Ngoc1Chi Dung Vu2Thi Thu Huong Nguyen3Huy Hoang Nguyen4Graduate University of Science and Technology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet str., Cau Giay, Hanoi 100000, VietnamCenter for Rare Diseases and Newborn Screening, Department of Endocrinology, Metabolism and Genetics, Vietnam National Children’s Hospital, 18/879 La Thanh str., Dong Da, Hanoi 100000, VietnamCenter for Rare Diseases and Newborn Screening, Department of Endocrinology, Metabolism and Genetics, Vietnam National Children’s Hospital, 18/879 La Thanh str., Dong Da, Hanoi 100000, VietnamGraduate University of Science and Technology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet str., Cau Giay, Hanoi 100000, VietnamGraduate University of Science and Technology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet str., Cau Giay, Hanoi 100000, VietnamMuscular dystrophies are a group of heterogeneous clinical and genetic disorders. Two siblings presented with characteristics like muscular dystrophy, abnormal white matter, and elevated serum creatine kinase level. The high throughput of whole exome sequencing (WES) makes it an efficient tool for obtaining a precise diagnosis without the need for immunohistochemistry. WES was performed in the two siblings and their parents, followed by prioritization of variants and validation by Sanger sequencing. Very rare variants with moderate to high predicted impact in genes associated with neuromuscular disorders were selected. We identified two pathogenic missense variants, c.778C>T (p.H260Y) and c.2987G>A (p.C996Y), in the <i>LAMA2 </i>gene (NM_000426.3), in the homozygous state in two siblings, and in the heterozygous state in their unaffected parents, which were confirmed by Sanger sequencing. Variant c.2987G>A has not been reported previously. These variants may lead to a change in the structure and function of laminin-α2, a member of the family of laminin-211, which is an extracellular matrix protein that functions to stabilize the basement membrane of muscle fibers during contractions. Overall, WES enabled an accurate diagnosis of both patients with <i>LAMA2</i>-related muscular dystrophy and expanded the spectrum of missense variants in <i>LAMA2</i>.https://www.mdpi.com/2075-4418/10/10/741LAMA2-related muscular dystrophyWES<i>LAMA2</i> variantsVietnamesec.778C&gt |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ngoc-Lan Nguyen Can Thi Bich Ngoc Chi Dung Vu Thi Thu Huong Nguyen Huy Hoang Nguyen |
spellingShingle |
Ngoc-Lan Nguyen Can Thi Bich Ngoc Chi Dung Vu Thi Thu Huong Nguyen Huy Hoang Nguyen Whole Exome Sequencing as a Diagnostic Tool for Unidentified Muscular Dystrophy in a Vietnamese Family Diagnostics LAMA2-related muscular dystrophy WES <i>LAMA2</i> variants Vietnamese c.778C& gt |
author_facet |
Ngoc-Lan Nguyen Can Thi Bich Ngoc Chi Dung Vu Thi Thu Huong Nguyen Huy Hoang Nguyen |
author_sort |
Ngoc-Lan Nguyen |
title |
Whole Exome Sequencing as a Diagnostic Tool for Unidentified Muscular Dystrophy in a Vietnamese Family |
title_short |
Whole Exome Sequencing as a Diagnostic Tool for Unidentified Muscular Dystrophy in a Vietnamese Family |
title_full |
Whole Exome Sequencing as a Diagnostic Tool for Unidentified Muscular Dystrophy in a Vietnamese Family |
title_fullStr |
Whole Exome Sequencing as a Diagnostic Tool for Unidentified Muscular Dystrophy in a Vietnamese Family |
title_full_unstemmed |
Whole Exome Sequencing as a Diagnostic Tool for Unidentified Muscular Dystrophy in a Vietnamese Family |
title_sort |
whole exome sequencing as a diagnostic tool for unidentified muscular dystrophy in a vietnamese family |
publisher |
MDPI AG |
series |
Diagnostics |
issn |
2075-4418 |
publishDate |
2020-09-01 |
description |
Muscular dystrophies are a group of heterogeneous clinical and genetic disorders. Two siblings presented with characteristics like muscular dystrophy, abnormal white matter, and elevated serum creatine kinase level. The high throughput of whole exome sequencing (WES) makes it an efficient tool for obtaining a precise diagnosis without the need for immunohistochemistry. WES was performed in the two siblings and their parents, followed by prioritization of variants and validation by Sanger sequencing. Very rare variants with moderate to high predicted impact in genes associated with neuromuscular disorders were selected. We identified two pathogenic missense variants, c.778C>T (p.H260Y) and c.2987G>A (p.C996Y), in the <i>LAMA2 </i>gene (NM_000426.3), in the homozygous state in two siblings, and in the heterozygous state in their unaffected parents, which were confirmed by Sanger sequencing. Variant c.2987G>A has not been reported previously. These variants may lead to a change in the structure and function of laminin-α2, a member of the family of laminin-211, which is an extracellular matrix protein that functions to stabilize the basement membrane of muscle fibers during contractions. Overall, WES enabled an accurate diagnosis of both patients with <i>LAMA2</i>-related muscular dystrophy and expanded the spectrum of missense variants in <i>LAMA2</i>. |
topic |
LAMA2-related muscular dystrophy WES <i>LAMA2</i> variants Vietnamese c.778C& gt |
url |
https://www.mdpi.com/2075-4418/10/10/741 |
work_keys_str_mv |
AT ngoclannguyen wholeexomesequencingasadiagnostictoolforunidentifiedmusculardystrophyinavietnamesefamily AT canthibichngoc wholeexomesequencingasadiagnostictoolforunidentifiedmusculardystrophyinavietnamesefamily AT chidungvu wholeexomesequencingasadiagnostictoolforunidentifiedmusculardystrophyinavietnamesefamily AT thithuhuongnguyen wholeexomesequencingasadiagnostictoolforunidentifiedmusculardystrophyinavietnamesefamily AT huyhoangnguyen wholeexomesequencingasadiagnostictoolforunidentifiedmusculardystrophyinavietnamesefamily |
_version_ |
1724645072902815744 |