Prenatal diagnosis of Duchenne muscular dystrophy revealed a novel mosaic mutation in Dystrophin gene: a case report
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CASE REPORT
Open Access
Prenatal diagnosis of Duchenne muscular dystrophy revealed a novel mosaic mutation in Dystrophin gene: a case report Yan Wang1,2,3,4*†, Yuhan Chen1,2,3,5†, San Mei Wang1,2,3,5†, Xin Liu1,2,3,5, Ya Nan Gu1,2,3,5 and Zhichun Feng1,2,3,5*
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. Keywords: Duchenne muscular dystrophy, Prenatal diagnosis, Dystrophin gene, Next-generation sequencing, Mosaicism
Background Duchenne muscular dystrophy (DMD, OMIM #310200) is a fatal X-linked recessive, inherited neuromuscular disorder characterized by muscle inflammation and progressive deterioration of muscle function [1–3]. The * Correspondence: [email protected]; [email protected] † Yan Wang, Yuhan Chen and San Mei Wang contributed equally to this work. 1 Department of Clinical Genetics, BaYi Children’s Hospital, Seventh Medical Center of Chinese PLA General Hospital, Beijing 100700, China 2 National Engineering Laboratory for Birth defects prevention and control of key technology, Beijing 100700, China Full list of author information is available at the end of the article
estimated incidence ranges from 10.71 to 27.78 per 100, 000 males [4, 5]. Patients with DMD primarily develop muscle weakness between the ages of 2–5 years, during which the symptoms slowly progress and render the patient immobile [6]. The mutation spectrum within the causative gene Dystrophin is complex and varies in types, sizes and locations, resulting in p
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