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Identification of Two Novel LAMA2 Mutations in a Chinese Patient with Congenital Muscular Dystrophy

Merosin-deficient CMD type 1A (MDC1A), caused by mutations of laminin subunit alpha 2 (LAMA2), is a predominant subtype of congenital muscular dystrophy (CMD). Herein, we described a Chinese patient with MDC1A who was admitted to hospital 17 days after birth because of marasmus and feeding difficult...

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Autores principales: Zhou, Jing, Tan, Jianxin, Ma, Dingyuan, Zhang, Jingjing, Cheng, Jian, Luo, Chunyu, Liu, Gang, Wang, Yuguo, Xu, Zhengfeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5816747/
https://www.ncbi.nlm.nih.gov/pubmed/29487616
http://dx.doi.org/10.3389/fgene.2018.00043
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author Zhou, Jing
Tan, Jianxin
Ma, Dingyuan
Zhang, Jingjing
Cheng, Jian
Luo, Chunyu
Liu, Gang
Wang, Yuguo
Xu, Zhengfeng
author_facet Zhou, Jing
Tan, Jianxin
Ma, Dingyuan
Zhang, Jingjing
Cheng, Jian
Luo, Chunyu
Liu, Gang
Wang, Yuguo
Xu, Zhengfeng
author_sort Zhou, Jing
collection PubMed
description Merosin-deficient CMD type 1A (MDC1A), caused by mutations of laminin subunit alpha 2 (LAMA2), is a predominant subtype of congenital muscular dystrophy (CMD). Herein, we described a Chinese patient with MDC1A who was admitted to hospital 17 days after birth because of marasmus and feeding difficulties. Mutations were identified by targeted capture and next generation sequencing (NGS) and further confirmed by Sanger sequencing. Paternity was confirmed by short tandem repeat analysis. Physical examination showed malnutrition, poor suck and appendicular hypotonia. Her serum CK levels were 2483 and 1962 U/L at 2 and 4 months of age, respectively. Brain magnetic resonance imaging performed at 1 month of age presented hyperintensity on T2-weighted images, T1-weighted images in parietal and occipital lobes, and diffusion-weighted image (DWI) as well as hypointensity on fluid attenuated inversion recovery (FLAIR) image; however, the cerebellum and corpus arenaceum were normal. At 7 months of age, delayed developmental milestones were observed, and she failed to turn her body over and raise her head up. A point mutation (c.1782+2T > G) and a frameshift duplication (c.8217dupT) in the LAMA2 gene were identified by targeted capture and NGS and further confirmed by Sanger sequencing. Moreover, genotyping with multiple short tandem repeat markers confirmed paternity to demonstrate that the point mutation is de novo. The frameshift duplication (c.8217dupT), inherited from her mother, was predicted to cause a substitution of Pro (P) to Ser (S) at the 2740th amino-acid residue and generate a prematurely truncated protein. The in silico analysis suggests that the mutation (c.1782+2T > G) may lead to aberrant splicing of LAMA2. Our case further confirms the heterogeneous clinical spectrum of MDC1A and presents two novel LAMA2 mutations to expand the mutation spectrum of MDC1A.
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spelling pubmed-58167472018-02-27 Identification of Two Novel LAMA2 Mutations in a Chinese Patient with Congenital Muscular Dystrophy Zhou, Jing Tan, Jianxin Ma, Dingyuan Zhang, Jingjing Cheng, Jian Luo, Chunyu Liu, Gang Wang, Yuguo Xu, Zhengfeng Front Genet Genetics Merosin-deficient CMD type 1A (MDC1A), caused by mutations of laminin subunit alpha 2 (LAMA2), is a predominant subtype of congenital muscular dystrophy (CMD). Herein, we described a Chinese patient with MDC1A who was admitted to hospital 17 days after birth because of marasmus and feeding difficulties. Mutations were identified by targeted capture and next generation sequencing (NGS) and further confirmed by Sanger sequencing. Paternity was confirmed by short tandem repeat analysis. Physical examination showed malnutrition, poor suck and appendicular hypotonia. Her serum CK levels were 2483 and 1962 U/L at 2 and 4 months of age, respectively. Brain magnetic resonance imaging performed at 1 month of age presented hyperintensity on T2-weighted images, T1-weighted images in parietal and occipital lobes, and diffusion-weighted image (DWI) as well as hypointensity on fluid attenuated inversion recovery (FLAIR) image; however, the cerebellum and corpus arenaceum were normal. At 7 months of age, delayed developmental milestones were observed, and she failed to turn her body over and raise her head up. A point mutation (c.1782+2T > G) and a frameshift duplication (c.8217dupT) in the LAMA2 gene were identified by targeted capture and NGS and further confirmed by Sanger sequencing. Moreover, genotyping with multiple short tandem repeat markers confirmed paternity to demonstrate that the point mutation is de novo. The frameshift duplication (c.8217dupT), inherited from her mother, was predicted to cause a substitution of Pro (P) to Ser (S) at the 2740th amino-acid residue and generate a prematurely truncated protein. The in silico analysis suggests that the mutation (c.1782+2T > G) may lead to aberrant splicing of LAMA2. Our case further confirms the heterogeneous clinical spectrum of MDC1A and presents two novel LAMA2 mutations to expand the mutation spectrum of MDC1A. Frontiers Media S.A. 2018-02-13 /pmc/articles/PMC5816747/ /pubmed/29487616 http://dx.doi.org/10.3389/fgene.2018.00043 Text en Copyright © 2018 Zhou, Tan, Ma, Zhang, Cheng, Luo, Liu, Wang and Xu. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Zhou, Jing
Tan, Jianxin
Ma, Dingyuan
Zhang, Jingjing
Cheng, Jian
Luo, Chunyu
Liu, Gang
Wang, Yuguo
Xu, Zhengfeng
Identification of Two Novel LAMA2 Mutations in a Chinese Patient with Congenital Muscular Dystrophy
title Identification of Two Novel LAMA2 Mutations in a Chinese Patient with Congenital Muscular Dystrophy
title_full Identification of Two Novel LAMA2 Mutations in a Chinese Patient with Congenital Muscular Dystrophy
title_fullStr Identification of Two Novel LAMA2 Mutations in a Chinese Patient with Congenital Muscular Dystrophy
title_full_unstemmed Identification of Two Novel LAMA2 Mutations in a Chinese Patient with Congenital Muscular Dystrophy
title_short Identification of Two Novel LAMA2 Mutations in a Chinese Patient with Congenital Muscular Dystrophy
title_sort identification of two novel lama2 mutations in a chinese patient with congenital muscular dystrophy
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5816747/
https://www.ncbi.nlm.nih.gov/pubmed/29487616
http://dx.doi.org/10.3389/fgene.2018.00043
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