Clinical and genetic analysis of a patient with HUPRA syndrome due to missense variants of SARS2 gene and literature review
黄娟 1李秋雨 2吉炜 3郭晓峰 4胡晓虹 5范姝婕
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作者信息
1. 福建省儿童医院心内科，福州 350011
2. 首都医科大学附属北京安贞医院心内科 北京市心肺血管病研究所，北京 100029
3. 上海交通大学医学院附属上海儿童医学中心心内科，上海 200127
4. 福建省妇幼保健院儿科，福州 350001
5. 上海交通大学医学院附属新华医院心内科，上海 200092
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摘要
目的 分析高尿酸血症-肺动脉高压-肾衰竭-碱中毒综合征（HUPRAS）的SARS2致病基因特定位点的致病性。 方法 选取2022年3月9日就诊于福建省儿童医院的HUPRAS患儿1例，对患儿进行临床和实验室检查，抽取患儿及其父母外周血进行全外显子基因变异检测，并对所筛选的变异进行Sanger测序验证及生物信息学分析。 结果 患儿男，6个月，其SARS2等位基因分别携带父系遗传的c.1205G>A/p.Arg402His变异和母系遗传的c.680G>A/p.Arg227Gln变异，其中c.680G>A既往未被报道。这两个变异人群频率极低，致病性软件预测其有害。Arg402和Arg227均进化高度保守，突变导致其编码的丝氨酰tRNA合成酶的氢键结构及疏水性均产生了变化，提示这两个变异能够解释患儿HUPRAS表型。 结论 SARS2基因的c.1205G>A/p.Arg402His和c.680G>A/p.Arg227Gln复合杂合变异可能导致HUPRAS。 Objective To explore the clinical manifestations and genotype of an infant with hyperuricemia, pulmonary hypertension, renal failure in infancy, and alkalosis syndrome (HUPRAS). Methods Clinical data of the patient were collected. Peripheral blood samples from the patient and his parents were acquainted for whole exome sequencing. The filtrated variants were verified by Sanger sequencing. The pathogenicity of the variants was predicted by bioinformatic tools. Results The patient is a male infant of 6 months old, carrying two missense variants in the SARS2 allele: a paternal inherited c.1205G>A (p. Arg402His) and a maternal inherited c.680G>A (p. Arg227Gln). The two variants were in extremely low population frequencies. The pathogenetic prediction tools categorized them as deleterious. Arg402 and Arg227 were highly conserved in evolution. The variants led to changes in the hydrogen bonds and hydrophobicity of seryl-tRNA synthetase encoded by SARS2. Conclusions c.1205G>A (p. Arg402His) and c.680G>A (p. Arg227Gln) are the possible causative variants of the HUPRA syndrome.
Abstract
Objective To explore the clinical manifestations and genotype of an infant with hyperuricemia, pulmonary hypertension, renal failure in infancy, and alkalosis syndrome (HUPRAS). Methods Clinical data of the patient were collected. Peripheral blood samples from the patient and his parents were acquainted for whole exome sequencing. The filtrated variants were verified by Sanger sequencing. The pathogenicity of the variants was predicted by bioinformatic tools. Results The patient is a male infant of 6 months old, carrying two missense variants in the SARS2 allele: a paternal inherited c.1205G>A (p. Arg402His) and a maternal inherited c.680G>A (p. Arg227Gln). The two variants were in extremely low population frequencies. The pathogenetic prediction tools categorized them as deleterious. Arg402 and Arg227 were highly conserved in evolution. The variants led to changes in the hydrogen bonds and hydrophobicity of seryl-tRNA synthetase encoded by SARS2. Conclusions c.1205G>A (p. Arg402His) and c.680G>A (p. Arg227Gln) are the possible causative variants of the HUPRA syndrome.
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