A Novel Mutation of SLC19A2 in a Chinese Zhuang Ethnic Family with Thiamine-Responsive Megaloblastic Anemia
| Autor: | Faquan Lin, Hongtao Li, Lin Liao, Jie Yan, Wei Shu, Xiao-ying Xian, Yuanyuan Qin, Jianming Luo |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Proband Male medicine.medical_specialty China Trma Anemia Megaloblastic Physiology Anemia Hearing Loss Sensorineural medicine.disease_cause lcsh:Physiology lcsh:Biochemistry 03 medical and health sciences chemistry.chemical_compound Exon Diabetes mellitus Asian People Internal medicine medicine Humans lcsh:QD415-436 Megaloblastic anemia Mutation biology lcsh:QP1-981 business.industry Infant Membrane Transport Proteins Thiamine Deficiency food and beverages Exons Visual impairment medicine.disease SLC19A2 mutation 030104 developmental biology Endocrinology chemistry SLC19A2 biology.protein Thiamine Female business human activities Thiamine pyrophosphate |
| Zdroj: | Cellular Physiology and Biochemistry, Vol 47, Iss 5, Pp 1989-1997 (2018) |
| ISSN: | 1421-9778 1015-8987 |
| Popis: | 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. Methods: 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). Results: 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. Conclusions: This novel homozygous mutation (c.1409insT) caused the onset of thiamine-responsive megaloblastic anemia in the proband. |
| Databáze: | OpenAIRE |
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