糖原贮积病：125 例患者队列中的 27 个新变异体。
Glycogen storage diseases: Twenty-seven new variants in a cohort of 125 patients.
机构信息
Post-Graduation Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Laboratory of Basic Research and Advanced Investigations in Neurosciences (BRAIN), Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
出版信息
Mol Genet Genomic Med. 2019 Nov;7(11):e877. doi: 10.1002/mgg3.877. Epub 2019 Sep 11.
BACKGROUND
Hepatic glycogen storage diseases (GSDs) are a group of rare genetic disorders in which glycogen cannot be metabolized to glucose in the liver because of enzyme deficiencies along the glycogenolytic pathway. GSDs are well-recognized diseases that can occur without the full spectrum, and with overlapping in symptoms.
METHODS
We analyzed a cohort of 125 patients with suspected hepatic GSD through a next-generation sequencing (NGS) gene panel in Ion Torrent platform. New variants were analyzed by pathogenicity prediction tools.
RESULTS
Twenty-seven new variants predicted as pathogenic were found between 63 variants identified. The most frequent GSD was type Ia (n = 53), followed by Ib (n = 23). The most frequent variants were p.Arg83Cys (39 alleles) and p.Gln347* (14 alleles) in G6PC gene, and p.Leu348Valfs (21 alleles) in SLC37A4 gene.
CONCLUSIONS
The study presents the largest cohort ever analyzed in Brazilian patients with hepatic glycogenosis. We determined the clinical utility of NGS for diagnosis. The molecular diagnosis of hepatic GSDs enables the characterization of diseases with similar clinical symptoms, avoiding hepatic biopsy and having faster results.
背景
肝糖原贮积病（GSD）是一组罕见的遗传性疾病，由于糖原代谢途径中的酶缺乏，肝脏无法将糖原代谢为葡萄糖。GSD 是一种公认的疾病，其临床表现可能不完整，且症状有重叠。
方法
我们通过 Ion Torrent 平台的下一代测序（NGS）基因面板分析了 125 例疑似肝 GSD 患者的队列。通过致病性预测工具分析新发现的变异。
结果
在 63 种已确定的变异中，发现了 27 种预测为致病性的新变异。最常见的 GSD 是 Ia 型（n=53），其次是 Ib 型（n=23）。最常见的变异是 G6PC 基因中的 p.Arg83Cys（39 个等位基因）和 p.Gln347*（14 个等位基因），以及 SLC37A4 基因中的 p.Leu348Valfs（21 个等位基因）。
结论
本研究展示了巴西肝糖原贮积症患者中分析过的最大队列。我们确定了 NGS 用于诊断的临床实用性。肝 GSD 的分子诊断能够对具有相似临床症状的疾病进行特征描述，避免肝活检并获得更快的结果。
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