| Title | Eleven novel mutations and clinical characteristics in seven Chinese patients with thiamine metabolism dysfunction syndrome |
| Authors | Li, Dongxiao Song, Jinqing Li, Xiyuan Liu, Yi Dong, Hui Kang, Lulu Liu, Yupeng Zhang, Yao Jin, Ying Guan, Hanzhou Zhou, Chongchen Yang, Yanling |
| Affiliation | Zhengzhou Univ, Henan Prov Key Lab Childrens Genet & Metab Dis, Childrens Hosp, Henan Childrens Hosp,Zhengzhou Childrens Hosp, Zhengzhou 450018, Peoples R China Peking Univ, Dept Pediat, Hosp 1, Beijing 100034, Peoples R China Childrens Hosp Shanxi Prov, Dept Pediat, Taiyuan, Peoples R China |
| Keywords | BASAL GANGLIA DISEASE EXOME SEQUENCING REVEALS PYROPHOSPHOKINASE DEFICIENCY EARLY-INFANTILE SLC19A3 DEFECTS IDENTIFICATION CHILDHOOD TRANSPORT SURVIVAL |
| Issue Date | Oct-2020 |
| Publisher | EUROPEAN JOURNAL OF MEDICAL GENETICS |
| Abstract | Thiamine metabolism dysfunction syndrome (THMD) comprises a group of clinically and genetically heterogeneous encephalopathies with autosomal recessive inheritance. Four genes, SLC19A3, SLC25A19, SLC19A2, and TPK1, are associated with this disorder. This study aimed to explore the clinical, biochemical and molecular characteristics of seven Chinese patients with THMD. Targeted next-generation sequencing of mitochondrial DNA and nuclear DNA was used to identify the causative mutations. The patients presented with subacute encephalopathy between the ages of 1-27 months. Brain magnetic resonance imaging (MRI) revealed abnormalities in the basal ganglia, indicating Leigh syndrome. Urine alpha-ketoglutarate in five patients was elevated. In four patients, five novel mutations (c.1276_1278delTAC, c.265A > C, c.197T > C, c.850T > C, whole gene deletion) were found in SLC19A3, which is associated with THMD2. In two patients, four novel mutations (c.194C > T, c.454C > A, c.481G > A, and c.550G > C) were identified in SLC25A19, supporting a diagnosis of THMD4. In one patient, two novel mutations (c.395T > C and c.614-1G > A) were detected in TPK1, which is indicative of THMD5. The patients received thiamine, biotin, and symptomatic therapy, upon which six patients demonstrated clinical improvement. Our findings expanded the phenotypic and genotypic spectrum of THMD, with eleven novel mutations identified in seven Chinese patients. Early diagnosis and treatment have a significant impact on prognosis. |
| URI | http://hdl.handle.net/20.500.11897/592242 |
| ISSN | 1769-7212 |
| DOI | 10.1016/j.ejmg.2020.104003 |
| Indexed | SCI(E) |
| Appears in Collections: | 第一医院 |
