Cargando…
Prenatal diagnosis of Duchenne muscular dystrophy revealed a novel mosaic mutation in Dystrophin gene: a case report
BACKGROUND: Duchenne muscular dystrophies (DMDs) are X-linked recessive neuromuscular disorders with malfunction or absence of the Dystrophin protein. Precise genetic diagnosis is critical for proper planning of patient care and treatment. In this study, we described a Chinese family with mosaic DMD...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7661169/ https://www.ncbi.nlm.nih.gov/pubmed/33176713 http://dx.doi.org/10.1186/s12881-020-01157-0 |
_version_ | 1783609156811358208 |
---|---|
author | Wang, Yan Chen, Yuhan Wang, San Mei Liu, Xin Gu, Ya Nan Feng, Zhichun |
author_facet | Wang, Yan Chen, Yuhan Wang, San Mei Liu, Xin Gu, Ya Nan Feng, Zhichun |
author_sort | Wang, Yan |
collection | PubMed |
description | BACKGROUND: Duchenne muscular dystrophies (DMDs) are X-linked recessive neuromuscular disorders with malfunction or absence of the Dystrophin protein. Precise genetic diagnosis is critical for proper planning of patient care and treatment. In this study, we described a Chinese family with mosaic DMD mutations and discussed the best method for prenatal diagnosis and genetic counseling of X-linked familial disorders. METHODS: We investigated all variants of the whole dystrophin gene using multiple DNA samples isolated from the affected family and identified two variants of the DMD gene in a sick boy and two female carriers by targeted next generation sequencing (TNGS), Sanger sequencing, and haplotype analysis. RESULTS: We identified the hemizygous mutation c.6794delG (p.G2265Efs*6) of DMD in the sick boy, which was inherited from his mother. Unexpectedly, a novel heterozygous mutation c.6796delA (p.I2266Ffs*5) of the same gene, which was considered to be a de novo variant, was detected from his younger sister instead of his mother by Sanger sequencing. However, further NGS analysis of the mother and her amniotic fluid samples revealed that the mother carried a low-level mosaic c.6796delA mutation. CONCLUSIONS: We reported two different mutations of the DMD gene in two siblings, including the novel mutation c.6796delA (p.I2266Ffs*5) inherited from the asymptomatic mosaic-carrier mother. This finding has enriched the knowledge of the pathogenesis of DMD. If no mutation is detected in obligate carriers, the administration of intricate STR/NGS/Sanger analysis will provide new ideas on the prenatal diagnosis of DMD. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12881-020-01157-0. |
format | Online Article Text |
id | pubmed-7661169 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-76611692020-11-13 Prenatal diagnosis of Duchenne muscular dystrophy revealed a novel mosaic mutation in Dystrophin gene: a case report Wang, Yan Chen, Yuhan Wang, San Mei Liu, Xin Gu, Ya Nan Feng, Zhichun BMC Med Genet Case Report BACKGROUND: Duchenne muscular dystrophies (DMDs) are X-linked recessive neuromuscular disorders with malfunction or absence of the Dystrophin protein. Precise genetic diagnosis is critical for proper planning of patient care and treatment. In this study, we described a Chinese family with mosaic DMD mutations and discussed the best method for prenatal diagnosis and genetic counseling of X-linked familial disorders. METHODS: We investigated all variants of the whole dystrophin gene using multiple DNA samples isolated from the affected family and identified two variants of the DMD gene in a sick boy and two female carriers by targeted next generation sequencing (TNGS), Sanger sequencing, and haplotype analysis. RESULTS: We identified the hemizygous mutation c.6794delG (p.G2265Efs*6) of DMD in the sick boy, which was inherited from his mother. Unexpectedly, a novel heterozygous mutation c.6796delA (p.I2266Ffs*5) of the same gene, which was considered to be a de novo variant, was detected from his younger sister instead of his mother by Sanger sequencing. However, further NGS analysis of the mother and her amniotic fluid samples revealed that the mother carried a low-level mosaic c.6796delA mutation. CONCLUSIONS: We reported two different mutations of the DMD gene in two siblings, including the novel mutation c.6796delA (p.I2266Ffs*5) inherited from the asymptomatic mosaic-carrier mother. This finding has enriched the knowledge of the pathogenesis of DMD. If no mutation is detected in obligate carriers, the administration of intricate STR/NGS/Sanger analysis will provide new ideas on the prenatal diagnosis of DMD. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12881-020-01157-0. BioMed Central 2020-11-11 /pmc/articles/PMC7661169/ /pubmed/33176713 http://dx.doi.org/10.1186/s12881-020-01157-0 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. 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 in a credit line to the data. |
spellingShingle | Case Report Wang, Yan Chen, Yuhan Wang, San Mei Liu, Xin Gu, Ya Nan Feng, Zhichun Prenatal diagnosis of Duchenne muscular dystrophy revealed a novel mosaic mutation in Dystrophin gene: a case report |
title | Prenatal diagnosis of Duchenne muscular dystrophy revealed a novel mosaic mutation in Dystrophin gene: a case report |
title_full | Prenatal diagnosis of Duchenne muscular dystrophy revealed a novel mosaic mutation in Dystrophin gene: a case report |
title_fullStr | Prenatal diagnosis of Duchenne muscular dystrophy revealed a novel mosaic mutation in Dystrophin gene: a case report |
title_full_unstemmed | Prenatal diagnosis of Duchenne muscular dystrophy revealed a novel mosaic mutation in Dystrophin gene: a case report |
title_short | Prenatal diagnosis of Duchenne muscular dystrophy revealed a novel mosaic mutation in Dystrophin gene: a case report |
title_sort | prenatal diagnosis of duchenne muscular dystrophy revealed a novel mosaic mutation in dystrophin gene: a case report |
topic | Case Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7661169/ https://www.ncbi.nlm.nih.gov/pubmed/33176713 http://dx.doi.org/10.1186/s12881-020-01157-0 |
work_keys_str_mv | AT wangyan prenataldiagnosisofduchennemusculardystrophyrevealedanovelmosaicmutationindystrophingeneacasereport AT chenyuhan prenataldiagnosisofduchennemusculardystrophyrevealedanovelmosaicmutationindystrophingeneacasereport AT wangsanmei prenataldiagnosisofduchennemusculardystrophyrevealedanovelmosaicmutationindystrophingeneacasereport AT liuxin prenataldiagnosisofduchennemusculardystrophyrevealedanovelmosaicmutationindystrophingeneacasereport AT guyanan prenataldiagnosisofduchennemusculardystrophyrevealedanovelmosaicmutationindystrophingeneacasereport AT fengzhichun prenataldiagnosisofduchennemusculardystrophyrevealedanovelmosaicmutationindystrophingeneacasereport |