Genotype/phenotype relationship in Gaucher disease patients. Novel mutation in glucocerebrosidase gene
Genotype/phenotype relationship in Gaucher disease patients. Novel mutation in glucocerebrosidase gene
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DOI：
10.1515/cclm-2020-0306
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发表时间：
2020-12-01
影响因子：
6.8
通讯作者：
Macher, Hada C.
中科院分区：
文献类型：
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作者：
Lepe-Balsalobre, Esperanza;Santotoribio, Jose D.;Macher, Hada C.
目的：戈谢病（GD）是最常见的遗传性溶酶体贮积病，由酸性β-葡萄糖苷酶（GBA）基因突变引起。本研究旨在确定GD患者的安达卢西亚突变及其基因型与表型的相关性。纳入了1999年至2019年诊断为GD的Virgen del Rocio大学医院患者。从数字病历中收集人口统计学和临床数据、β-葡萄糖脑苷脂酶活性、GBA基因致病性变异和用于监测治疗的生物标志物。在GBA基因中共鉴定出6个致病性突变和1个未在上文中描述的突变[c.937T>C（p.Tyr313His）]，其中4例为纯合子，22例为复合杂合子。24例患者被诊断为非神经病变形式（1型），2例患者出现神经系统受累（2型或3型）。最常见的变异是c.1226A>G（p.Asn409Ser），在24例患者中检测到，其次是c.1448T>C（p.Leu483Pro）变异，在13例患者中检测到。c.1448T>C（p.Leu483Pro）突变出现在与2型和3型GD相关的神经系统受累的最严重表型中，而c.1226A>G（p.Asn409Ser）突变与神经系统改变无关。结论：c.1226A>G（p.Asn409Ser）和c.1448T>C（p.Leu483Pro）突变是最常见的突变类型。c.937T>C（p.Tyr313His）是一种新的突变。c.1448T>C（p.Leu483Pro）突变与神经功能改变相关，而c.1226A>G（p.Asn409Ser）突变与神经功能改变无关。
Objectives: Gaucher disease (GD) is the most common inherited lysosomal storage disease, caused by mutations in acid beta-glucosidase (GBA) gene. This study aimed to identify mutations in Andalusia patients with GD and their genotype-phenotype correlation.Methods: Descriptive observational study. University Hospital Virgen del Rocio patients diagnosed from GD from 1999 to 2019 were included. Demographic and clinical data, beta-glucocerebrosidase activity, variants pathogenic in GBA gene and biomarkers for monitoring treatment were collected from digital medical record.Results: Twenty-six patients with aged between 1 day and 52 years were studied. A total of six mutations described as pathogenic and one mutation not described above [c.937T>C (p.Tyr313His)] were identified in the GBA gene, four patients were homozygotes and 22 compound heterozygotes. Twenty-four patients were diagnosed in non-neuropathic form (type 1) and two cases presented neurological involvement (type 2 or 3). The most common variant was c.1226A>G (p.Asn409Ser), which was detected in 24 patients, followed by c.1448T>C (p.Leu483Pro) variant, identified in 13 patients. The c.1448T>C (p.Leu483Pro) mutation has been presented in the most severe phenotypes with neurological involvement associated with type 2 and 3 GD, while c.1226A>G (p.Asn409Ser) mutation has not been associated with neurological alterations. Splenomegaly and bone disease were the most frequent clinical manifestations, and thrombocytopenia was the most common hematological disorder.Conclusions: The c.1226A>G (p.Asn409Ser) and c.1448T>C (p.Leu483Pro) mutations were the most common. The c.937T>C (p.Tyr313His) was identified as a novel mutation. The c.1448T>C (p.Leu483Pro) mutation was associated with neurological alterations and c.1226A>G (p.Asn409Ser) mutation has not been associated it.