Yorkshire Regional Genetics Service, Chapel Allerton Hospital, Leeds Teaching Hospitals NHS Trust, Chapeltown Road, Leeds, West Yorkshire LS7 4SA, United Kingdom.
Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health & Great Ormond Street Hospital, London, United Kingdom.
Neuromuscul Disord. 2021 Apr;31(4):359-366. doi: 10.1016/j.nmd.2020.09.033. Epub 2020 Oct 3.
Pathogenic variants in TPM2 have been associated with a variable clinical spectrum, including congenital myopathies and distal arthrogryposis, all but one with dominant inheritance. We report the second case of recessively inherited TPM2-related Escobar variant of multiple pterygium syndrome and congenital myopathy in a patient from a consanguineous family. Ultra-structural examination of the biopsy revealed few cores/mini-cores and sparse nemaline rods. We found a novel homozygous intronic sequence variant, c.564-2A>C in TPM2. This variant is predicted to abolish the consensus acceptor splice site for exon 6b of TPM2 gene. Parents of the proband, both healthy adults with no clinical features, were heterozygous for the variant. Here we establish a homozygous intronic variant in TPM2 as the likely cause of Escobar variant of multiple pterygium syndrome and congenital myopathy, with sparse nemaline rods.
TPM2 中的致病性变异与可变的临床谱相关，包括先天性肌病和远端关节挛缩症，但除了一种以外，均为显性遗传。我们报告了第二个隐性遗传 TPM2 相关 Escobar 变异型多发性翼状胬肉综合征和先天性肌病的病例，该病例来自一个近亲家庭。活检的超微结构检查显示很少有核心/迷你核心和稀疏的杆状体。我们发现了一种新的纯合内含子序列变异，即 TPM2 中的 c.564-2A>C。该变体预计会破坏 TPM2 基因外显子 6b 的一致受体剪接位点。先证者的父母均为健康成年人，无临床特征，该变体杂合。在这里，我们确定 TPM2 中的纯合内含子变异是导致多发性翼状胬肉综合征和先天性肌病伴稀疏杆状的 Escobar 变异的可能原因。
