Abstract：
Here, we described three affected boys from two unrelated families of Ossetian-Digor origin from the Republic of North Ossetia-Alania who were admitted to the Research Centre for Medical Genetics with unspecified muscular dystrophy. High-throughput sequencing was performed and revealed two novel frameshift variants in the COL6A2 gene (NM_001849.3) in a heterozygous state each in both cases: c.508_535delinsCTGTGG and c.1659_1660del (case 1) and c.1689del and c.1659_1660del (case 2). In two cases, the same nucleotide variant in the COL6A2 gene (c.1659_1660del) was observed. We have suggested that the variant c.1659_1660del may be common in the Ossetian-Digor population because two analyzed families have the same ancestry from the same subethnic group of Ossetians). The screening for an asymptomatic carriage of the nucleotide variant c.1659_1660del in 54 healthy donors from Ossetian-Digor population revealed that the estimated carrier frequency is 0.0093 (CI: 0.0002-0.0505), which is high for healthy carriers of the pathogenic variant. Molecular genetic, anamnestic data and clinical examination results allowed us to diagnose Ullrich muscular dystrophy in those affected boys. Genetic heterogeneity and phenotypic diversity of muscular dystrophies complicate diagnosis. It is important to make a differential diagnosis of such conditions and use HTS methods to determine the most accurate diagnosis.
摘要：
这里,我们描述了三个受影响的男孩，他们来自北奥塞梯-阿拉尼亚共和国的两个不相关的Ossetian-Digor家族，他们因未指定的肌营养不良而被纳入医学遗传学研究中心。进行了高通量测序，并在两种情况下都揭示了COL6A2基因（NM_001849.3）中处于杂合状态的两个新的移码变体：c.508_535delinsCTGTGG和c.1659_1660del（案例1）和c.1689del和c.1659_1660del（案例2）。在两种情况下，在COL6A2基因中观察到相同的核苷酸变体(c.1659_1660del)。我们已经建议，变体c.1659_1660del在奥塞梯-Digor人口中可能很常见，因为两个被分析的家庭具有来自奥塞梯人的同一亚种族群体的相同祖先）。在来自奥塞梯-迪戈尔人群的54名健康供体中，对核苷酸变体c.1659_1660del的无症状携带进行的筛查表明，估计的载波频率为0.0093（CI：0.0002-0.0505），这对于致病性变异的健康携带者来说是很高的。分子遗传学,记忆数据和临床检查结果使我们能够诊断受影响男孩的Ullrich肌营养不良。肌营养不良的遗传异质性和表型多样性使诊断复杂化。重要的是对此类疾病进行鉴别诊断并使用HTS方法来确定最准确的诊断。
