Compound heterozygous POMT1 mutations in a Chinese family with autosomal recessive muscular dystrophy-dystroglycanopathy C1.
Compound heterozygous POMT1 mutations in a Chinese family with autosomal recessive muscular dystrophy-dystroglycanopathy C1.
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DOI：
10.1111/jcmm.13068
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发表时间：
2017-07
影响因子：
5.3
通讯作者：
Deng H
中科院分区：
文献类型：
--
作者：
Hu P;Wu S;Yuan L;Lin Q;Zheng W;Xia H;Xu H;Guan L;Deng H
肌营养不良-糖链营养不良(MDDG)是一组遗传性和临床异质性的肌肉疾病，以先天性肌营养不良或迟发性肢体带状肌营养不良为特征，并伴有脑部和眼部异常，由α-营养不良糖基化异常引起。对一个常染色体隐性遗传性MDDG家系进行了外显子组测序和Sanger测序。O-甘露糖基转移酶1基因(POMT1)的复合杂合突变c.1338+1G>；A(p.H415Kfs*3)和c.1457G>；C(p.W486S，rs746849558)是其遗传原因。表现为较轻的MDDG的患者，表现为晚发的进行性骨盆近端、肩带和四肢肌肉无力、关节痉挛、智力低下和肌酸激酶升高，没有脑或眼结构异常，进一步被基因诊断为MDDGC1。POMT1基因剪接点突变(c.1338+1G>；A)导致外显子13跳跃，导致蛋白截短，可能导致严重的表型，而等位基因错义突变(p.W486S)可能降低MDDG的严重程度。这些发现可能扩大POMT1基因的表型和突变谱。临床诊断辅以分子筛查可能导致对这种疾病更准确的诊断、预后和改善的遗传咨询。
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.