Abstract：
Congenital muscular dystrophies (CMD) are a group of heterogeneous disorders. Here, targeted next generation sequencing of 168 CMD-associated genes was performed on collected clinic samples to identify potential mutations. A loss-of-function mutation (c.4676-4682delGCTGCAA; p.Cys1560Thrfs*33) of the LAMA2 gene in a consanguineous family was identified and confirmed by Sanger sequencing. The second recessive mutation in SYNE1 (c.2881C>T; p.Arg961Trp) was found in the SAP motif, which was predicted to be involved in chromosomal organization. The third homozygous mutation (c.32462C>T; p.Pro10821Leu) in TTN was mapped to the third PPAK motif of the encoded protein. Muscle biopsies of the proband showed large variations in muscle fiber size, necrotic and regenerating fibers and an increase in endomysial collagen tissue. To the best of our knowledge, this is the first case with CMD and mildly enlarged heart, carrying three novel recessive mutations in LAMA2, SYNE1, and TTN.
摘要：
先天性肌营养不良（CMD）是一组异质性疾病。这里,对收集的临床样本进行168个CMD相关基因的靶向下一代测序,以鉴定潜在突变.鉴定了近亲家族中LAMA2基因的功能丧失突变（c.4676-4682delGCTGCAA；p.Cys1560Thrfs*33），并通过Sanger测序进行了确认。在SAP基序中发现SYNE1的第二个隐性突变（c.2881C>T;p.Arg961Trp），预测与染色体组织有关。TTN中的第三个纯合突变(c.32462C>T;p.Pro10821Leu)被定位到编码蛋白的第三个PPAK基序。先证者的肌肉活检显示肌纤维大小有很大差异，坏死和再生纤维以及肌内胶原组织的增加。据我们所知,这是第一个CMD心脏轻度增大的病例,在LAMA2、SYNE1和TTN中携带三个新的隐性突变。
