Xian Xiaoying, Liao Lin, Shu Wei, Li Hongtao, Qin Yuanyuan, Yan Jie, Luo Jianming, Lin Fa-Quan
Department of Clinical Laboratory, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Department of Cell Biology and Genetics, Guangxi Medicinal University, Nanning, China.
Cell Physiol Biochem. 2018;47(5):1989-1997. doi: 10.1159/000491467. Epub 2018 Jul 3.
BACKGROUND/AIMS: Thiamine-responsive megaloblastic anemia syndrome is a rare autosomal recessive disorder resulting from mutations in SLC19A2, and is mainly characterized by megaloblastic anemia, diabetes, and progressive sensorineural hearing loss.
We study a Chinese Zhuang ethnicity family with thiamine-responsive megaloblastic anemia. The proband of the study presented with anemia and diabetes, similar to his late brother, as well as visual impairment. All clinical manifestations were corrected with thiamine (30 mg/d) supplementation for 1-3 months, except for visual impairment, which was irreversible. The presence of mutations in all exons and the flanking sequences of the SLC19A2 gene were analyzed in this family based on the proband's and his brother's clinical data. Computer analysis and prediction of the protein conformation of mutant THTR-1. The relative concentration of thiamine pyrophosphate in the proband's whole blood before and after initiation of thiamine supplement was measured by high performance liquid chromatography (HPLC).
Gene sequencing showed a homozygous mutation in exon 6 of the SLC19A2 gene (c.1409insT) in the proband. His parents and sister were diagnosed as heterozygous carriers of the c.1409insT mutation. Computer simulation showed that the mutations caused a change in protein conformation. HPLC results suggested that the relative concentration of thiamine pyrophosphate in the proband's whole blood after thiamine supplement was significantly different (P=0.016) from that at baseline.
This novel homozygous mutation (c.1409insT) caused the onset of thiamine-responsive megaloblastic anemia in the proband.
背景/目的：硫胺素反应性巨幼细胞贫血综合征是一种罕见的常染色体隐性疾病，由SLC19A2基因突变引起，主要特征为巨幼细胞贫血、糖尿病和进行性感音神经性听力损失。
我们研究了一个患有硫胺素反应性巨幼细胞贫血的中国壮族家庭。该研究的先证者表现出贫血和糖尿病，与他已故的哥哥相似，还伴有视力障碍。除了不可逆的视力障碍外，所有临床表现通过补充硫胺素（30mg/d）1至3个月后得到纠正。基于先证者及其哥哥的临床数据，对该家庭中SLC19A2基因的所有外显子及其侧翼序列进行了突变分析。对突变型THTR-1的蛋白质构象进行计算机分析和预测。通过高效液相色谱法（HPLC）测定先证者补充硫胺素前后全血中硫胺素焦磷酸的相对浓度。
基因测序显示先证者的SLC19A2基因第6外显子存在纯合突变（c.1409insT）。他的父母和姐姐被诊断为c.1409insT突变的杂合携带者。计算机模拟显示这些突变导致了蛋白质构象的改变。HPLC结果表明，先证者补充硫胺素后全血中硫胺素焦磷酸的相对浓度与基线时相比有显著差异（P = 0.016）。
这种新的纯合突变（c.1409insT）导致了先证者发生硫胺素反应性巨幼细胞贫血。
