Open AccessWhole exome sequencing identified a novel DAG 1 mutation in a patient with rare, mild and late age of onset muscular dystrophy‐dystroglycanopathy
Author(s) -
Dai Yi,
Liang Shengran,
Dong Xue,
Zhao Yanhuan,
Ren Haitao,
Guan Yuzhou,
Yin Haifang,
Li Chen,
Chen Lin,
Cui Liying,
Banerjee Santasree
Publication year - 2019
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13979
Subject(s) - missense mutation , proband , muscular dystrophy , limb girdle muscular dystrophy , genetics , congenital muscular dystrophy , exome sequencing , dysferlin , biology , mutation , dystrophin , compound heterozygosity , sanger sequencing , gene
Muscular dystrophy‐dystroglycanopathy (limb‐girdle), type C, 9 ( MDDGC 9) is the rarest type of autosomal recessive muscular dystrophies. MDDGC 9 is manifested with an early onset in childhood. Patients with MDDGC 9 usually identified with defective glycosylation of DAG 1, hence it is known as “dystroglycanopathies”. Here, we report a Chinese pedigree presented with mild MDDGC 9. The proband is a 64 years old Chinese man. In this family, both the proband and proband's younger brother have been suffering from mild and late onset MDDGC 9. Muscle biopsy showed that the left deltoid muscle with an advanced stage of dystrophic change. Immunohistochemistry staining of dystrophin, α‐sarcoglycan, β‐sarcoglycan and dysferlin are normal. Molecular genetic analysis of the proband has been done with whole exome sequencing. A homozygous novel missense mutation (c.2326C>T; p.R776C) in the exon 3 of the DAG 1 gene has been identified in the proband. Sanger sequencing revealed that this missense mutation is co‐segregated well among the affected and unaffected (carrier) family members. This mutation is not detected in 200 normal healthy control individuals. This novel homozygous missense mutation (c.2326C>T) causes substitution of arginine by cystine at the position of 776 (p.R776C) which is evolutionarily highly conserved. Immunoblotting studies revealed that a significant reduction of α‐dystroglycan expression in the muscle tissue. The novelty of our study is that it is a first report of DAG 1 associated muscular dystrophy‐dystroglycanopathy (limb‐girdle), type C, 9 ( MDDGC 9) with mild and late age of onset. In Chinese population this is the first report of DAG 1 associated MDDGC 9.