Abstract：
Limb girdle muscular dystrophy (LGMD) type 2G is a rare form of muscle disease, described only in a few patients worldwide, caused by mutations in TCAP gene, encoding the protein telethonin. It is characterised by proximal limb muscle weakness associated with distal involvement of lower limbs, starting in the first or second decade of life. We describe the case of a 37-year-old woman of Greek origin, affected by disto-proximal lower limb weakness. No cardiac or respiratory involvement was detected. Muscle biopsy showed myopathic changes with type I fibre hypotrophy, cytoplasmic vacuoles, lipid overload, multiple central nuclei and fibre splittings; ultrastructural examination showed metabolic abnormalities. Next generation sequencing analysis detected a homozygous frameshift mutation in the TCAP gene (c.90_91del), previously described in one Turkish family. Immunostaining and Western blot analysis showed complete absence of telethonin. Interestingly, Single Nucleotide Polymorphism analysis of the 10 Mb genomic region containing the TCAP gene showed a shared homozygous haplotype of both the Greek and the Turkish patients, thus suggesting a possible founder effect of TCAP gene c.90_91del mutation in this part of the Mediterranean area.
摘要：
肢体带型肌营养不良症（LGMD）2G型是一种罕见的肌肉疾病，仅在全球少数患者中描述，由TCAP基因突变引起的，编码蛋白质的端黄素。它的特点是与下肢远端受累相关的近端肢体肌肉无力，从人生的第一个或第二个十年开始。我们描述了一个37岁的希腊裔妇女的案例，受近端的下肢无力影响。未检测到心脏或呼吸受累。肌肉活检显示肌病性改变伴有I型纤维肥大，细胞质液泡，脂质超负荷,多个中央核和纤维分裂；超微结构检查显示代谢异常。下一代测序分析检测到TCAP基因的纯合移码突变（c.90_91del），以前在一个土耳其家庭中描述过。免疫染色和Western印迹分析显示完全不存在端黄素。有趣的是,包含TCAP基因的10Mb基因组区域的单核苷酸多态性分析显示，希腊和土耳其患者均具有纯合单倍型，因此表明TCAP基因c.90_91del突变在地中海地区的这一部分可能的创始人效应。
