%0 Generic %A H.M.J., Hussain %A G., Murtaza %A X., Jiang %A R., Khan %A M., Khan %A M.B.S., Kakakhel %A T., Khan %A F., Wahab %A H., Zhang %A Y., Zhang %A M.B., Khan %A P., Ahmed %A H., Ma %A Z., Xu %D 2019 %T Supplementary Material for: Whole Exome Sequencing Revealed a Novel Nonsense Variant in the GNRHR Gene Causing Normosmic Hypogonadotropic Hypogonadism in a Pakistani Family %U https://karger.figshare.com/articles/dataset/Supplementary_Material_for_Whole_Exome_Sequencing_Revealed_a_Novel_Nonsense_Variant_in_the_b_i_GNRHR_i_b_Gene_b_i_i_b_Causing_Normosmic_Hypogonadotropic_Hypogonadism_in_a_Pakistani_Family/7951961 %R 10.6084/m9.figshare.7951961.v1 %2 https://karger.figshare.com/ndownloader/files/14802335 %2 https://karger.figshare.com/ndownloader/files/14802338 %K Congenital hypogonadotropic hypogonadism %K Gonadotropin-releasing hormone %K GNRHR %K Nonsense mutation %K Normosmic hypogonadotropic hypogonadism %X Background: Congenital hypogonadotropic hypogonadism (CHH) is a heterogeneous disorder characterized by delayed or loss of puberty and infertility due to functional deficiency in the hypothalamic gonadotropin-releasing hormone (GnRH). CHH can be classified into 2 subtypes on the basis of olfaction: Kallmann syndrome and normosmic CHH (nCHH). The spectrum of genetic variants causing CHH is continually expanding. Here, we recruited a consanguineous Pakistani family having 2 male and 2 female infertile patients diagnosed with idiopathic nCHH. Aims: The aim of this study was to investigate the genetic cause of nCHH in the family. Methods: Clinical and physical analyses were performed for the patients. Genetic analysis was carried out using whole exome and Sanger sequencing. Results: Clinical and physical investigations confirmed low levels of gonadotropins and failure of secondary sexual development in the patients. Genetic analysis identified a novel nonsense mutation (chr4: g.68619942G>A, c.112C>T, p.Arg38*) in the gonadotropin-releasing hormone receptor gene (GNRHR) recessively co-segregating with nCHH in this family. All the patients are homozygous and their parents are heterozygous carriers, while normal siblings are heterozygous carriers or wild-type for this mutation, indicating that the identified mutation is pathogenic for nCHH in the family. Conclusion: We report the first homozygous nonsense mutation in the GNRHR gene (chr4: g. 68619942G>A, c.112C>T, p. Arg38*) that is associated with familial nCHH. Hence, our study displayed a good correlation of the genotype and phenotype of nCHH patients. %I Karger Publishers