五例Kallmann综合征患者的基因型-表型关系和遗传学研究  

Genotype-phenotype and genetic analysis in five patients with Kallmann syndrome

作　　者：夏俊珂 罗晓 吴静[2] 代鹏[1] 刘艳霞[3] 夏艳洁 夏培苡 孔祥东[1] Junke Xia;Xiao Luo;Jing Wu;Peng Dai;Yanxia Liu;Yanjie Xia;Peiyi Xia;Xiangdong Kong(Prenatal and Genetic Diagnosis Center,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China;Department of Pediatrics,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China;Department of Metabolism and Endocrinology,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China;Department of Pathology,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)

机构地区：[1]郑州大学第一附属医院妇产科遗传与产前诊断中心,450052 [2]郑州大学第一附属医院儿科,450052 [3]郑州大学第一附属医院内分泌与代谢科,450052 [4]郑州大学第一附属医院病理科,450052

出　　处：《中华内分泌代谢杂志》2021年第12期1106-1111,共6页Chinese Journal of Endocrinology and Metabolism

基　　金：国家重点研发计划(2018YFC1002203)。

摘　　要：探讨Kallmann综合征患者的基因型-表型关系,研究其基因突变谱和遗传学特点。分析5例Kallmann综合征患者的临床资料,采用染色体核型分析、全外显子测序(WES)和多重连接探针扩增技术(MLPA)进行遗传学检测。患者就诊年龄为2月龄至45岁,均为男性。3/5例因隐睾就诊,1例因性腺发育不良就诊,1例因空腹血糖高就诊。患者表现为低促伴嗅觉缺失,磁共振成像(MRI)示双侧嗅球嗅束未见显示(未发育),染色体核型均为46 XY。5例患者均检测到Kallmann综合征相关基因变异,且均为新发现的变异。嗅觉因子1(ANOS1)基因c.1795_1799del(p.Asn599Profs*66)变异的1例患者伴右肾发育不全。染色质解旋酶DNA结合蛋白7(CHD7)基因c.2824A>G(p.Thr942Ala)变异的1例患者具有临床异质性和不完全外显。此外,WES提示Xp22.31(chrX:8507699-8507804)区域约109 bp的缺失,通过MLPA验证为ANOS1基因10号外显子半合子缺失,该变异来源母亲,符合X连锁隐性遗传。Kallmann综合征具有高度的遗传异质性和临床异质性。早期进行WES,有助于确诊,必要时进行MLPA和基因组拷贝数变异(CNV)分析。To study the genotype-phenotype and genetic characteristics of Kallmann syndrome.Five patients with Kallmann syndrome were enrolled.Clinical data collection,chromosome karyotyping,whole exome sequencing(WES),and multiplex ligation-dependent probe amplification(MLPA)were used.All the five patients were males,aging from 2 months to 45 years old.Three of the five patients complained cryptorchidism,one complained gonadal dysgenesis,and one complained fasting hyperglycemia.The clinical feature was hypogonadotropic hypogonadism with anosmia,and all karyotype was 46 XY.Magnetic resonance imaging(MRI)showed undeveloped olfactory bulbs and tracts.Kallmann syndrome related gene novel variants were found in all the 5 patients.The hypoplasia of right kidney was found in a patient with c.1795_1799del(p.Asn599Profs*66)of anosmin 1(ANOS1)variant.Clinical heterogeneity and incomplete penetrance were seen in a patient with c.2824A>G(p.Thr942Ala)of chromodomain helicase DNA binding protein 7(CHD7).Besides,WES indicated a 109 bp-deletion on Xp22.31(chrX:8507699-8507804),which was the deletion of exon 10 on ANOS1 gene verified by MLPA.The deletion variant was inherited form his mother,and conformed to X-linked recessive inheritance.Kallmann syndrome is genetic and clinical heterogeneous.WES is helpful for early diagnosis.MLPA and genome copy number variation analysis(CNV)are also recommend if necessary.

关 键 词：KALLMANN综合征 低促性腺激素性腺功能减退 嗅觉缺失 全外显子测序 

分 类 号：R596[医药卫生—内科学]