Analysis of clinical characteristics and genetic variants in a child with Isolated sulfite oxidase deficiency
杨志刚 1权亚丽 2王媛 1陈国洪 1马燕丽 1徐凯丽 1张丽玲
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作者信息
1. 1河南省儿童医院神经科，郑州 450053
2. 2洛阳市妇幼保健院儿科重症监护室，洛阳 471099
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摘要
目的 对1例亚硫酸盐氧化酶缺乏症(ISOD)患儿的临床特征及基因变异进行分析，明确其可能的致病原因。 方法 选取在2019年3月就诊于河南省儿童医院的1例患儿作为研究对象。采用目标区域捕获对患儿及父母进行全外显子组测序，按照美国医学遗传学与基因组学学会(ACMG)的基因变异解读标准和指南对基因变异进行致病性评估。 结果 基因检测结果显示患儿SUOX基因存在c.1200C>G(p.Tyr400*)和c.1406_1421delCCTGGCAGGTGGCTAA(p.Thr469Serfs*20)复合杂合变异，患儿母亲携带c.1200C>G(p.Tyr400*)杂合变异，父亲携带c.1406_1421delCCTGGCAGGTGGCTAA(p.Thr469Serfs*20)杂合变异。其中c.1200C>G为已报道过的致病性变异，而c.1406_1421del CCTGGCAGGTGGCTAA未见报道，根据ACMG变异解读标准和指南，该变异判定为致病性变异(PVS1+PM2_Supporting+PM3)。 结论 SUOX基因c.1200C>G和c.1406_1421delCCTGGCAGGTGGCTAA变异可能为该例ISOD患儿的致病原因，本研究扩展了SUOX基因变异谱，为患儿的临床诊断及该家系的遗传咨询提供了依据。 Objective To explore the genetic basis for a child with Isolated sulfite oxidase deficiency(ISOD). Methods The child and her parents were subjected to targeted capture and next-generation sequencing. Pathogenicity of candidate variants was assessed based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). Results The child was found to harbor compound heterozygous variants of the SUOX gene, namely c. 1200C>G (p.Tyr400*) and c. 1406_1421delCCTGGCAGGTGGCTAA (p.Thr469Serfs*20), which were inherited from her mother and father, respectively. The c. 1200C>G was a known pathogenic variant, while c. 1406_1421delCCTGGCAGGTGG CTAA was unreported previously and predicted to be a pathogenic variant (PVS1+ PM2_Supporting+ PM3) based on the guidelines from the American College of Medical Genetics and Genomics. Conclusion The compound c. 1200C>G and c. 1406_1421delCCTGGCAGGTGGCTAA variants of theSUOX gene probably underlay the pathogenesis of ISOD in this child. Above finding has expanded the spectrum of SUOX gene variants and provided molecular evidence for the clinical diagnosis and genetic counseling for this pedigree.
Abstract
Objective To explore the genetic basis for a child with Isolated sulfite oxidase deficiency(ISOD). Methods The child and her parents were subjected to targeted capture and next-generation sequencing. Pathogenicity of candidate variants was assessed based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). Results The child was found to harbor compound heterozygous variants of the SUOX gene, namely c. 1200C>G (p.Tyr400*) and c. 1406_1421delCCTGGCAGGTGGCTAA (p.Thr469Serfs*20), which were inherited from her mother and father, respectively. The c. 1200C>G was a known pathogenic variant, while c. 1406_1421delCCTGGCAGGTGG CTAA was unreported previously and predicted to be a pathogenic variant (PVS1+ PM2_Supporting+ PM3) based on the guidelines from the American College of Medical Genetics and Genomics. Conclusion The compound c. 1200C>G and c. 1406_1421delCCTGGCAGGTGGCTAA variants of theSUOX gene probably underlay the pathogenesis of ISOD in this child. Above finding has expanded the spectrum of SUOX gene variants and provided molecular evidence for the clinical diagnosis and genetic counseling for this pedigree.
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