An isolated hypogonadotropic hypogonadism male with a novel de novoFGFR1mutation fathered a normal son evidenced by prenatal genetic diagnosis
An isolated hypogonadotropic hypogonadism male with a novel de novoFGFR1mutation fathered a normal son evidenced by prenatal genetic diagnosis
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产前基因诊断证实，一名患有新型 FGFR1 突变的孤立性低促性腺激素性性腺功能减退症男性生下了一个正常的儿子
作者：
Xu Hao;Li Zongzhe;Sun Taotao;Chen Yingwei;Wang Daoqi;Wang Tao;Wang Shaogang;Liu Jihong
孤立性低促性腺激素性性腺功能减退症（IHH）是一种罕见但可治疗的男性不育症，由促性腺激素释放激素（GnRH）分泌或作用的先天性缺陷引起。我们报告了一个中国IHH男性与一个新的FGFR 1突变谁成功地父亲一个正常的儿子。使用从家系中提取的DNA进行靶向下一代测序、生物信息学分析和桑格测序。患者接受促性腺激素治疗，并在治疗期间使其妻子受孕。在妊娠18周时进行羊膜穿刺术。在该患者的FGFR 1基因（NM_001174067.1）第8外显子中发现了一种新的致病性错义突变（c.980A>G，p.Asn327Ser），而在其正常父母中未发现。该变体在从穿刺样本获得的DNA中也不存在。他的儿子在2岁时生长发育正常。这是IHH家族中首例基于下一代靶向测序和桑格测序相结合对IHH父亲进行基因检测的产前基因诊断。我们扩展了IHH患者FGFR 1的突变谱。根据遗传学检测结果进行产前基因诊断，有助于对IHH家系进行遗传咨询。
Isolated hypogonadotropic hypogonadism (IHH) is a rare but treatable form of male infertility caused by congenital defect in gonadotropin‐releasing hormone (GnRH) secretion or action. We report a Chinese IHH male with a novelFGFR1mutation who successfully fathered a normal son. Targeted next‐generation sequencing, bioinformatics analysis and Sanger sequencing were performed by using the DNA extracted from the pedigree. The patient was treated with gonadotropin and was able to impregnant his wife during the treatment. Amniocentesis was performed at the 18 weeks of gestation. A novel de novo pathogenic missense variant (c.980A>G, p.Asn327Ser) in exon 8 inFGFR1gene (NM_001174067.1) was identified in the patient but not in his normal parents. This variant was also absent in the DNA obtained from the amniocentesis sample. His son has normal growth and development at the age of 2 years. This is the first case of prenatal genetic diagnosis based on the genetic testing of the IHH father by combining targeted next‐generation and Sanger sequencing in IHH family. We extended the mutation spectrum ofFGFR1in IHH patients. Prenatal genetic diagnosis based on the results of genetic testing of the IHH patients may be helpful in the genetic counselling for the IHH families.