CHD7基因变异致特发性低促性腺激素型性腺功能减退症1例的临床特点与遗传学分析

Clinical feature and genetic analysis of a patient with Idiopathic hypogonadotropic hypogonadism due to a novel variant of CHD7 gene

目的探讨1例CHD7基因变异所致嗅觉正常的特发性低促性腺激素性腺功能减退症(nIHH)患儿的临床及遗传学特征。方法以2022年10月就诊于安徽省儿童医院的1例nIHH患儿作为研究对象。对其进行全外显子组测序。对候选变异进行Sanger测序家系验证以及生物信息学分析。结果患儿主要表现为第二性征发育迟缓,但嗅觉功能未见异常。基因检测提示患者CHD7基因存在c.3052C>T(p.Pro1018Ser)杂合变异,其父母该位点均为野生型。该变异在PubMed及HGMD数据库均未见收录。同源性分析提示相关位点在进化中高度保守,蛋白质模拟分析提示可能破坏局部结构的稳定性。根据美国医学与遗传学学会变异指南,该变异评级为可能致病性变异(PS2+PM2_Supporting+PP2+PP3+PP4)。结论该患者第二性征发育迟缓表现可能缘于CHD7基因的变异。上述发现进一步拓展了CHD7基因的变异谱。

Objective To explore the clinical feature and genetic etiology of a patient with normosmic idiopathic hypogonadotropic hypogonadism(nIHH)due to variant of CHD7 gene.Methods A patient who had presented at Anhui Provincial Children′s Hospital in October 2022 was selected as the study subject.Clinical data of the patient was collected.The patient and his parents were subjected to trio-whole exome sequencing.Candidate variant was verified by Sanger sequencing and bioinformatic analysis.Results The patient had featured delayed development of secondary sexual characteristics but normal olfactory function.Genetic testing revealed that he has harbored a c.3052C>T(p.Pro1018Ser)missense variant of the CHD7 gene,for which both of his parents were of the wild type.The variant has not been recorded in the PubMed and HGMD databases.Analysis of amino acid sequences suggested that the variant site is highly conserved,and the variant may affect the stability of protein structure.Based on the guidelines from the American College of Medical Genetics and Genomics,the c.3032C>T variant was classified as a likely pathogenic(PS2+PM2_Supporting+PP2+PP3+PP4).Conclusion The delayed development of secondary sexual characteristics of the patient may be attributed to the c.3052C>T(p.Pro1018Ser)variant of the CHD7 gene.Above finding has expanded the variation spectrum of the CHD7 gene.