Related Experiment Video
Updated: Apr 16, 2026
HOX Loci Focused CRISPR/sgRNA Library Screening Identifying Critical CTCF Boundaries
Published on: March 31, 2019
Homozygous loss-of-function mutations in SOHLH1 in patients with nonsyndromic hypergonadotropic hypogonadism
Yavuz Bayram1, Suleyman Gulsuner, Tulay Guran
1Department of Molecular and Human Genetics (Y.B., T.Ga., M.M.A., E.K., D.P., J.R.L.), Baylor College of Medicine, Houston, Texas 77030; Department of Medicine, Division of Medical Genetics (S.G., H.U.G., S.B.P., M.L., T.W., M.-C.K.), University of Washington, Seattle, Washington 98195; Department of Pediatric Endocrinology and Diabetes (T.Gu., Z.A., S.T., A.Be.), Marmara University Hospital, Istanbul, Turkey 34899; Department of Pediatric Endocrinology (A.Ab., E.Bob., A.Bu.), Dokuz Eylül University Faculty of Medicine, Izmir, Turkey 35340; Department of Medical Genetics (G.Y.), Bezmialem University, Istanbul, Turkey 34093; Human Genome Sequencing Center (S.N.J., D.M., E.Boe., R.A.G.), Baylor College of Medicine, Houston, Texas 77030; Human Genetics Center (E.Boe.), University of Texas Health Science Center at Houston, Houston, Texas 77030; Department of Pediatrics (J.R.L.), Baylor College of Medicine, Houston, Texas 77030; and Texas Children's Hospital (J.R.L.), Houston, Texas 77030.
Context:
Hypergonadotropic hypogonadism presents in females with delayed or arrested puberty, primary or secondary amenorrhea due to gonadal dysfunction, and is further characterized by elevated gonadotropins and low sex steroids. Chromosomal aberrations and various specific gene defects can lead to hypergonadotropic hypogonadism. Responsible genes include those with roles in gonadal development or maintenance, sex steroid synthesis, or end-organ resistance to gonadotropins. Identification of novel causative genes in this disorder will contribute to our understanding of the regulation of human reproductive function.
Objectives:
The aim of this study was to identify and report the gene responsible for autosomal-recessive hypergonadotropic hypogonadism in two unrelated families.
Design And Participants:
Clinical evaluation and whole-exome sequencing were performed in two pairs of sisters with nonsyndromic hypergonadotropic hypogonadism from two unrelated families.
Results:
Exome sequencing analysis revealed two different truncating mutations in the same gene: SOHLH1 c.705delT (p.Pro235fs*4) and SOHLH1 c.27C>G (p.Tyr9stop). Both mutations were unique to the families and segregation was consistent with Mendelian expectations for an autosomal-recessive mode of inheritance.
Conclusions:
Sohlh1 was known from previous mouse studies to be a transcriptional regulator that functions in the maintenance and survival of primordial ovarian follicles, but loss-of-function mutations in human females have not been reported. Our results provide evidence that homozygous-truncating mutations in SOHLH1 cause female nonsyndromic hypergonadotropic hypogonadism.
Related Concept Videos
01:43Sex-linked Disorders
01:33Pleiotropy
02:41Lethal Alleles
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
01:21Nondisjunction
01:29Nondisjunction
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...