生物素-硫铵素反应性基底节病一家系SLC19A3基因的两个新变异

Identification of two novel SLC19A3 variants in a Chinese patient with Biotin-thiamine responsive basal ganglia disease

目的分析1例表现为全面发育落后患儿的遗传学病因。方法对患儿进行临床和实验室检査,应用二代目标区域捕获测序技术对患儿进行神经系统疾病相关基因的检测,对可疑变异位点进行保守性及致病性预测,并进行患儿及其父母的Sanger测序验证。结果患儿临床表现为发育迟缓,独坐不稳,不能区分生熟人。基因检测示患儿SLC19A3基因存在c.448G>A和c.169OT,二者均为未见报道的变异,两个变异位置编码的氨基酸为蛋白的保守位点,生物学软件预测具有致病性。结论SLC19A3基因的c.448OA和c.169C>T复合杂合变异丰富了SLC19A3基因的变异数据库,该基因复合杂合变异引起生物素-硫铵素反应性基底节病,可能导致患儿发病。

Objective To explore the genetic basis for a neonate featuring global developmental delay.Methods Clinical and laboratory tests were carried out for the patient.Peripheral venous blood samples were collected from the neonate and his parents for the extraction of DNA.Potential variant was detected by using targeted capture and next generation sequencing for a panel of genes associated with nervous system diseases.Suspected variant was validated by Sanger sequencing.Results The nine-month-old boy manifested global developmental delay and was unstable to sit alone and distinguish strangers from acquaintance.Genetic testing revealed two novel variants of the SLC19A3 gene in him,namely c.448G>A and c.169C>T.The amino acids encoded by the two codons are highly conservative,and both variants were predicted to be pathogenic by bioinformatic analysis.Conclusion The compound heterozygous c.4480*A and c.169C>T variants probably underlay the onset of disease in the patient.Above finding also enriched the variant spectrum o£SLC19A3 gene underlying Biotin-thiamine responsive basal ganglia disease.