A novel SLC37A4 missense mutation in GSD-Ib without hepatomegaly causes enhanced leukocytes endoplasmic reticulum stress and apoptosis
发布时间：2021-06-03
点击次数：
影响因子：1.995
发表刊物：Mol Genet Genomic Med.
关键字：G6PT, glycogen storage disease type Ib, gout, leukocytopenia, SLC37A4
摘要：Background Glycogen storage disease (GSD) type Ib is an autosomal recessive disease caused by defects of glucose‐6‐phosphate transporter (G6PT), encoded by the SLC37A4 gene. To date, over 100 mutations have been revealed in the SLC37A4 gene. GSD‐Ib patients manifest a metabolic phenotype of impaired blood glucose homeostasis and also carry the additional complications of neutropenia and myeloid dysfunction. Methods Here, we present two daughters with an initial diagnosis of gout in a Chinese consanguineous family. Whole‐exome sequencing was performed to identify the mutations. The mechanism of leukocytopenia was investigated. Results Whole‐exome sequencing analysis of the proband identified a novel homozygous p.P119L mutation in SLC37A4, leading to a diagnosis of GSD‐Ib. We found that the potential pathogenic p.P119L mutation leads to an unusual phenotype characterized by gout at onset, and GSD‐Ib arising from this variant also manifests multiple metabolic abnormalities, leukocytopenia, and anemia, but no hepatomegaly. The leukocytes from the proband showed increased mRNA levels of sXBP‐1, BIP, and CHOP genes in the unfolded protein response pathway, and enhanced Bax mRNA and caspase‐3 activity, which might contribute to leukocytopenia. Conclusion Our findings broaden the variation spectrum of SLC37A4 and suggest no strict genotype–phenotype correlations in GSD‐Ib patients.
合写作者：Haiyan Tang,Liping Duan,Xiaoxia Zuo,Xiaoliu Shi,Yisha Li,Hongjun Zhao
第一作者：Qianyun Xu
论文类型：基础研究
通讯作者：Huali Zhang（通讯作者）
学科门类：医学
一级学科：基础医学
期号：2021 Jan;9(1):e1568.
是否译文：否
发表时间：2020-12-05
收录刊物：SCI