Western Australian Institute for Medical Research and the Centre for Medical Research, University of Western Australia, Nedlands, Western Australia, Australia.
Neuromuscul Disord. 2013 Feb;23(2):165-9. doi: 10.1016/j.nmd.2012.11.005. Epub 2012 Dec 3.
The clinically and genetically heterogenous foetal akinesias have low rates of genetic diagnosis. Exome sequencing of two siblings with phenotypic lethal multiple pterygium syndrome identified compound heterozygozity for a known splice site mutation (c.691+2T>C) and a novel missense mutation (c.956A>G; p.His319Arg) in glycogen branching enzyme 1 (GBE1). GBE1 mutations cause glycogen storage disease IV (GSD IV), including a severe foetal akinesia sub-phenotype. Re-investigating the muscle pathology identified storage material, consistent with GSD IV, which was confirmed biochemically. This study highlights the power of exome sequencing in genetically heterogeneous diseases and adds multiple pterygium syndrome to the phenotypic spectrum of GBE1 mutation.
临床和遗传异质性的胎儿运动不能被诊断的情况很常见。对患有表型致死性多发翼状胬肉综合征的两兄弟进行外显子组测序，发现糖基化酶 1（GBE1）中存在已知剪接突变（c.691+2T>C）和新型错义突变（c.956A>G；p.His319Arg）的复合杂合性。GBE1 突变导致糖原贮积症 IV（GSD IV），包括严重的胎儿运动不能亚表型。重新研究肌肉病理学发现了与 GSD IV 一致的贮积物，通过生化方法得到了证实。本研究突出了外显子组测序在遗传异质性疾病中的作用，并将多发翼状胬肉综合征添加到 GBE1 突变的表型谱中。
