Wang Juanjuan, He Xiaoliang, Chen Denghuan, Hang Shouwei, Gao Yutong, Li Xu, Hu Kefei, Bai Chuanqing, Chen Yuqing
Department of Endocrinology, Rheumatism and Immunology, Anhui Provincial Children's Hospital, Hefei, Anhui 230051, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2021 Oct 10;38(10):977-980. doi: 10.3760/cma.j.cn511374-20200716-00517.
To detect variant of TRNT1 gene in a child featuring sideroblastic anemia with B-cell immunodeficiency, periodic fever and developmental delay (SIFD).
The proband and his parents were analyzed through trio-whole exome sequencing. Sanger sequencing and bioinformatic analysis were carried out to verify the candidate variant sites associated with the clinical phenotype.
Genetic testing showed that the proband has carried compound heterozygous variants of the TRNT1 gene, namely c.88A>G(p.Met30Val) and c.363G>T(p.Glu121Asp). Sanger sequencing confirmed that the variants were respectively inherited from his father and mother. The variants were unreported previously. By bioinformatic analysis, both variants were predicted to affect the stability of binding of the TRNT1 protein with tRNA. Based on the American College of Medical Genetics and Genomics standards and guidelines, c.88A>G and c.363G>T variants of TRNT1 gene were predicted to be uncertain significance (PM2+PP3+PP4) and likely pathogenic (PM1+PM2+PP3+PP4), respectively.
The c.88A>G (p.Met30Val) and c.363G>T(p.Glu121Asp) compound heterozygous variants of the TRNT1 gene probably underlay the disease in this patient. Above finding has enriched the spectrum of TRNT1 gene variants.
检测一名患有铁粒幼细胞贫血伴B细胞免疫缺陷、周期性发热和发育迟缓（SIFD）患儿的TRNT1基因变异。
通过三联体全外显子测序分析先证者及其父母。进行Sanger测序和生物信息学分析以验证与临床表型相关的候选变异位点。
基因检测显示先证者携带TRNT1基因的复合杂合变异，即c.88A>G（p.Met30Val）和c.363G>T（p.Glu121Asp）。Sanger测序证实这些变异分别遗传自他的父亲和母亲。这些变异此前未被报道。通过生物信息学分析，预测这两个变异均会影响TRNT1蛋白与tRNA结合的稳定性。根据美国医学遗传学与基因组学学会的标准和指南，TRNT1基因的c.88A>G和c.363G>T变异分别被预测为意义未明（PM2+PP3+PP4）和可能致病（PM1+PM2+PP3+PP4）。
TRNT1基因的c.88A>G（p.Met30Val）和c.363G>T（p.Glu121Asp）复合杂合变异可能是该患者疾病的病因。上述发现丰富了TRNT1基因变异谱。
