Abstract：
New techniques in molecular genetic diagnostics now allow for accurate diagnosis in a large proportion of patients with muscular diseases. Nevertheless, many patients remain unsolved, although the clinical history and/or the muscle biopsy give a clear indication of the involved genes. In many cases, there is a strong suspicion that the cause must lie in unexplored gene areas, such as deep-intronic or other non-coding regions. In order to find these changes, next-generation sequencing (NGS) methods are constantly evolving, making it possible to sequence entire genomes to reveal these previously uninvestigated regions. Here, we present a young woman who was strongly suspected of having a so far genetically unsolved sarcoglycanopathy based on her clinical history and muscle biopsy. Using short read whole genome sequencing (WGS), a homozygous inversion on chromosome 13 involving SGCG and LINC00621 was detected. The breakpoint in intron 2 of SGCG led to the absence of γ-sarcoglycan, resulting in the manifestation of autosomal recessive limb-girdle muscular dystrophy 5 (LGMDR5) in the young woman.
摘要：
分子遗传诊断的新技术现在可以在大部分肌肉疾病患者中进行准确的诊断。然而，许多患者仍未解决，尽管临床病史和/或肌肉活检清楚地表明了相关基因。在许多情况下,人们强烈怀疑原因一定在于未开发的基因区域，如深内含子或其他非编码区。为了找到这些变化，下一代测序(NGS)方法在不断发展，使得对整个基因组进行测序以揭示这些以前未被研究的区域成为可能。这里,我们介绍了一名年轻女性，根据她的临床病史和肌肉活检，她被强烈怀疑患有迄今为止尚未解决的基因上未解决的肌糖病变。使用短读取全基因组测序（WGS），在涉及SGCG和LINC00621的13号染色体上检测到纯合倒位。SGCG内含子2的断点导致γ-肌聚糖的缺失,导致年轻女性常染色体隐性遗传肢带肌营养不良5（LGMDR5）的表现。
