一例卡尔曼综合征并45,X/46,XY嵌合体患者的遗传学分析

Analysis of a patient with Kallmann syndrome and a 45,X/46,XY karyotype

目的对一例性腺功能低下伴嗅觉减退并45,X/46,XY嵌合体的卡尔曼综合征(Kallmann syndrome,KS)患者进行基因变异分析,明确其致病原因。方法收集患者及父母外周静脉血样行基因测序分析,并通过Sanger测序进行家系分析及位点验证。结果患者存在PROKR2基因c.533G>C(p.W178S)、c.308C>T(p.A103V)复合变异。Sanger测序结果显示父亲携带c.533G>C(p.W178S)杂合变异,母亲携带c.308C>T(p.A103V)杂合变异。c.533G>C(p.W178S)为可疑致病变异,c.308C>T(p.A103v)为临床意义不明确的变异。结论本例45,X/46,XY嵌合体患者异常性染色体数目减少并未造成生物功能方面的改变。在临床工作中应提高对KS的认识和鉴别诊治。对于临床考虑诊断为KS的患者,早期完善基因检测有助于明确诊治、判断预后、遗传咨询及后期随访管理。

Objective To explore the etiology of a patient with Kallmann syndrome(congenital hypogonadism and anosmia)and a 45,X/46,XY karyotype.Methods Peripheral venous blood samples were collected from the proband and his parents and subjected to whole exome sequencing.Candidate variants were verified by Sanger sequencing.Results The proband was found to harbor compound heterozygous variants of the PROKR2 gene,namely c.533G>C(p.W178S)and c.308C>T(p.A103V),which were inherited from his father and mother,respectively.The two variants were respectively predicted to be likely pathogenic and variant of unknown significance.Conclusion The sex chromosomal mosaicism might have caused no particular clinical manifestations in this patient.For patients with features of Kallmann syndrome,genetic testing is conducive to early diagnosis and can provide a basis for genetic counseling and clinical treatment.