Compound heterozygous POMT1 mutations in a Chinese family with autosomal recessive muscular dystrophy-dystroglycanopathy C1.
Muscular dystrophy-dystroglycanopathy (MDDG) is a genetically and clinically heterogeneous group of muscular disorders, characterized by congenital muscular dystrophy or later-onset limb-girdle muscular dystrophy accompanied by brain and ocular abnormalities, resulting from aberrant alpha-dystroglycan glycosylation. Exome sequencing and Sanger sequencing were performed on a six-generation consanguineous Han Chinese family, members of which had autosomal recessive MDDG. Compound heterozygous mutations, c.1338+1G>A (p.H415Kfs*3) and c.1457G>C (p.W486S, rs746849558), in the protein O-mannosyltransferase 1 gene (POMT1), were identified as the genetic cause. Patients that exhibited milder MDDG manifested as later-onset progressive proximal pelvic, shoulder girdle and limb muscle weakness, joint contractures, mental retardation and elevated creatine kinase, without structural brain or ocular abnormalities, were further genetically diagnosed as MDDGC1. The POMT1 gene splice-site mutation (c.1338+1G>A) which leads to exon 13 skipping and results in a truncated protein may contribute to a severe phenotype, while the allelic missense mutation (p.W486S) may reduce MDDG severity. These findings may expand phenotype and mutation spectrum of the POMT1 gene. Clinical diagnosis supplemented with molecular screening may result in more accurate diagnoses of, prognoses for, and improved genetic counselling for this disease.
Center for Experimental Medicine and Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha, China.
Pengzhi
P
Hu
Department of Orthopedics, The Third Xiangya Hospital, Central South University, Changsha, China.
Song
S
Wu
Center for Experimental Medicine and Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha, China.
Lamei
L
Yuan
BGI-Shenzhen, Shenzhen, China.
Qiongfen
Q
Lin
Center for Experimental Medicine and Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha, China.
Wen
W
Zheng
Center for Experimental Medicine and Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha, China.
Hong
H
Xia
Center for Experimental Medicine and Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha, China.
Hongbo
H
Xu
BGI-Shenzhen, Shenzhen, China.
Liping
L
Guan
Center for Experimental Medicine and Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha, China.
Hao
H
Deng
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D003241:Consanguinity; D004252:DNA Mutational Analysis; D059472:Exome / Q000235:genetics*; D005260:Female; D005817:Genetic Counseling; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D008297:Male; D008364:Mannosyltransferases / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D022821:RNA Splice Sites / Q000235:genetics; D058494:Walker-Warburg Syndrome / Q000235:genetics* / Q000503:physiopathology
D022821:RNA Splice Sites; D008364:Mannosyltransferases; C082696:protein O-mannosyltransferase
POMT1 gene; exome sequencing; genetic counselling; muscular dystrophy-dystroglycanopathy; mutation