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An isolated hypogonadotropic hypogonadism male with a novel de novo FGFR1 mutation fathered a normal son evidenced by prenatal genetic diagnosis
Author(s) -
Xu Hao,
Li Zongzhe,
Sun Taotao,
Chen Yingwei,
Wang Daoqi,
Wang Tao,
Wang Shaogang,
Liu Jihong
Publication year - 2020
Publication title -
andrologia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.633
H-Index - 59
eISSN - 1439-0272
pISSN - 0303-4569
DOI - 10.1111/and.13821
Subject(s) - sanger sequencing , missense mutation , proband , genetic counseling , amniocentesis , hypogonadotropic hypogonadism , prenatal diagnosis , medicine , genetics , infertility , consanguinity , exome sequencing , mutation , endocrinology , exon , biology , pregnancy , gene , hormone , fetus
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 novel FGFR1 mutation 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 in FGFR1 gene (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 of FGFR1 in 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.