%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