PDF(Pubmed)
Abstract：
Combined oxidative phosphorylation deficiency 35 (COXPD35) is a rare autosomal recessive disorder associated with homozygous or compound heterozygous mutations in the tRNA isopentenyltransferase (TRIT1) gene in chromosome 1p34.2. To date, only 10 types of allelic variants in the TRIT1 gene have been previously reported in 9 patients with COXPD35. Herein, we describe a case with a novel homozygous missense variant in TRIT1. A 6-year, 6-month-old boy presented with global developmental delay, microcephaly, intractable seizures, and failure to thrive. The other main clinical manifestations were intellectual disability, spastic tetraparesis, truncal hypotonia, malnutrition, polyuria and polydipsia, ketotic hypoglycemia, dysmorphic facial features, strabismus, bicuspid aortic valve, and nephrolithiasis. The detailed biochemical, radiological, and metabolic evaluations were unremarkable. Chromosomal analysis confirmed a normal male 46,XY karyotype and the array comparative genomic hybridization analysis revealed no abnormalities. We identified a novel homozygous missense variant of c.246G>C (p.Met82Ile) in the TRIT1 gene, and the variant was confirmed by Sanger sequencing. The present case is the first report describing strabismus, ketotic hypoglycemia, nephrolithiasis, and bicuspid aortic valve in TRIT1-related COXPD35. This study expands the genotype-phenotype spectrum of TRIT1-related COXPD35.
摘要：
联合氧化磷酸化缺陷35（COXPD35）是一种罕见的常染色体隐性遗传疾病，与染色体1p34.2中tRNA异戊烯基转移酶（TRIT1）基因的纯合或复合杂合突变有关。迄今为止,先前在9例COXPD35患者中仅报道了TRIT1基因中的10种等位基因变异.在这里，我们描述了一个在TRIT1中具有新的纯合错义变体的案例。六年，6个月大的男孩出现了全球发育迟缓，小头畸形,顽固性癫痫发作,未能茁壮成长。其他主要临床表现为智力障碍，痉挛性四轻瘫,躯干肌张力减退,营养不良,多尿和多饮，酮症性低血糖,畸形面部特征，斜视,二叶主动脉瓣,和肾结石。详细的生化，放射学,代谢评估并不显著。染色体分析证实了正常男性46，XY核型，阵列比较基因组杂交分析未发现异常。我们鉴定了c.246G>C的新型纯合错义变体（p。Met82Ile）在TRIT1基因中，变异体通过Sanger测序证实。这个病例是第一个描述斜视的报告,酮症性低血糖,肾结石,和TRIT1相关COXPD35的二叶主动脉瓣。这项研究扩展了TRIT1相关COXPD35的基因型-表型谱。
