Prenatal diagnosis of Duchenne muscular dystrophy revealed a novel mosaic mutation in Dystrophin gene: a case report
Abstracts 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 m...
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| Format: | Article |
| Language: | English |
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BMC
2020-11-01
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| Series: | BMC Medical Genetics |
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| Online Access: | http://link.springer.com/article/10.1186/s12881-020-01157-0 |
| _version_ | 1829521831781990400 |
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| author | Yan Wang Yuhan Chen San Mei Wang Xin Liu Ya Nan Gu Zhichun Feng |
| author_facet | Yan Wang Yuhan Chen San Mei Wang Xin Liu Ya Nan Gu Zhichun Feng |
| author_sort | Yan Wang |
| collection | DOAJ |
| description | Abstracts 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. |
| first_indexed | 2024-12-16T15:22:02Z |
| format | Article |
| id | doaj.art-51f19fdca79f4faca7efe17698aa79c9 |
| institution | Directory Open Access Journal |
| issn | 1471-2350 |
| language | English |
| last_indexed | 2024-12-16T15:22:02Z |
| publishDate | 2020-11-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medical Genetics |
| spelling | doaj.art-51f19fdca79f4faca7efe17698aa79c92022-12-21T22:26:36ZengBMCBMC Medical Genetics1471-23502020-11-0121111010.1186/s12881-020-01157-0Prenatal diagnosis of Duchenne muscular dystrophy revealed a novel mosaic mutation in Dystrophin gene: a case reportYan Wang0Yuhan Chen1San Mei Wang2Xin Liu3Ya Nan Gu4Zhichun Feng5Department of Clinical Genetics, BaYi Children’s Hospital, Seventh Medical Center of Chinese PLA General HospitalDepartment of Clinical Genetics, BaYi Children’s Hospital, Seventh Medical Center of Chinese PLA General HospitalDepartment of Clinical Genetics, BaYi Children’s Hospital, Seventh Medical Center of Chinese PLA General HospitalDepartment of Clinical Genetics, BaYi Children’s Hospital, Seventh Medical Center of Chinese PLA General HospitalDepartment of Clinical Genetics, BaYi Children’s Hospital, Seventh Medical Center of Chinese PLA General HospitalDepartment of Clinical Genetics, BaYi Children’s Hospital, Seventh Medical Center of Chinese PLA General HospitalAbstracts 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.http://link.springer.com/article/10.1186/s12881-020-01157-0Duchenne muscular dystrophyPrenatal diagnosisDystrophin geneNext-generation sequencingMosaicism |
| spellingShingle | Yan Wang Yuhan Chen San Mei Wang Xin Liu Ya Nan Gu Zhichun Feng Prenatal diagnosis of Duchenne muscular dystrophy revealed a novel mosaic mutation in Dystrophin gene: a case report BMC Medical Genetics Duchenne muscular dystrophy Prenatal diagnosis Dystrophin gene Next-generation sequencing Mosaicism |
| 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 | Duchenne muscular dystrophy Prenatal diagnosis Dystrophin gene Next-generation sequencing Mosaicism |
| url | http://link.springer.com/article/10.1186/s12881-020-01157-0 |
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