The Folkhaelsan Department of Medical Genetics, The Folkhaelsan Institute of Genetics and the Department of Medical and Clinical Genetics, University of Helsinki, Helsinki, Finland; Children's Hospital, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
John Walton Muscular Dystrophy Research Centre, Institute of Genetic Medicine, Newcastle University, Newcastle upon-Tyne, United Kingdom.
Neuromuscul Disord. 2018 Jul;28(7):614-618. doi: 10.1016/j.nmd.2018.04.012. Epub 2018 May 16.
We describe two Finnish siblings in whom an incidentally detected elevated creatine kinase activity eventually led to a diagnosis of limb-girdle muscular dystrophy-dystroglycanopathy (Type C12; MDDGC12). When diagnosed at age 10 and 13 years, they were mildly affected with a slow or non-progressive disease course. The main symptoms comprised infrequent hip cramps triggered by flexion, neck cramps triggered by yawning, transient growing pains, calf hypertrophy and mild proximal muscle weakness. Their cognitive and motor developments were unremarkable and they were physically active. Whole-exome sequencing revealed compound heterozygous mutations, both of which were novel, in the protein O-mannosyl kinase (POMK) gene in both siblings; a missense mutation, p.Pro322Leu (c.965C > T), and a nonsense mutation, p.Arg46Ter (c.136C > T). The results were confirmed by Sanger sequencing, showing that the parents were heterozygous carriers of one mutation each. This report adds to the literature by providing phenotype and genotype data on this ultra-rare POMK-related dystroglycanopathy.
我们描述了两名芬兰同胞，他们的肌酸激酶活性升高是偶然发现的，最终被诊断为肢带型肌营养不良症-糖蛋白聚糖病（C12 型；MDDGC12）。他们在 10 岁和 13 岁时被诊断出来，病情较轻，呈缓慢或非进行性发展。主要症状包括由弯曲引起的髋关节痉挛、打哈欠引起的颈部痉挛、短暂的生长痛、小腿肥大和轻度近端肌无力。他们的认知和运动发育正常，身体活跃。全外显子组测序显示，这对同胞兄妹均在蛋白 O-甘露糖基激酶（POMK）基因中存在复合杂合突变，均为新突变；一个错义突变，p.Pro322Leu（c.965C>T），和一个无义突变，p.Arg46Ter（c.136C>T）。结果通过 Sanger 测序得到证实，表明父母各携带一种突变的杂合子。该报告通过提供这种超罕见的 POMK 相关糖蛋白聚糖病的表型和基因型数据，为文献增添了内容。
