• PMID: 25636053
• Gene Name: IL17RD
• Condition: Idiopathic hypogonadotropic hypogonadism (IHH)
• Association: In pedigrees with an IHH proband, the proband's variant was shared by 53% (10/19) of DP family members vs 12% (4/33) of unaffected family members (P = .003). In DP subjects with no family history of IHH, 14% (8/56) had potentially pathogenic variants in I
• Population size: 963
• Population details: 963 (75 Idiopathic hypogonadotropic hypogonadism (IHH), 888 controls)
• Sex: Male, Female
• Infertility type: Male infertility, Female infertility
• Associated genes: IL17RD, TAC3
• Other associated phenotypes: Idiopathic hypogonadotropic hypogonadism (IHH)

A shared genetic basis for self-limited delayed puberty and idiopathic hypogonadotropic hypogonadism

Zhu J, Choa RE, Guo MH, Plummer L, Buck C, Palmert MR, Hirschhorn JN, Seminara SB, Chan YM.

CONTEXT: Delayed puberty (DP) is a common issue and, in the absence of an underlying condition, is typically self limited. Alhough DP seems to be heritable, no specific genetic cause for DP has yet been reported. In contrast, many genetic causes have been found for idiopathic hypogonadotropic hypogonadism (IHH), a rare disorder characterized by absent or stalled pubertal development. OBJECTIVE: The objective of this retrospective study, conducted at academic medical centers, was to determine whether variants in IHH genes contribute to the pathogenesis of DP. SUBJECTS AND OUTCOME MEASURES: Potentially pathogenic variants in IHH genes were identified in two cohorts: 1) DP family members of an IHH proband previously found to have a variant in an IHH gene, with unaffected family members serving as controls, and 2) DP individuals with no family history of IHH, with ethnically matched control subjects drawn from the Exome Aggregation Consortium. RESULTS: In pedigrees with an IHH proband, the proband's variant was shared by 53% (10/19) of DP family members vs 12% (4/33) of unaffected family members (P = .003). In DP subjects with no family history of IHH, 14% (8/56) had potentially pathogenic variants in IHH genes vs 5.6% (1 907/33 855) of controls (P = .01). Potentially pathogenic variants were found in multiple DP subjects for the genes IL17RD and TAC3. CONCLUSIONS: These findings suggest that variants in IHH genes can contribute to the pathogenesis of self-limited DP. Thus, at least in some cases, self-limited DP shares an underlying pathophysiology with IHH. FAU - Zhu, Jia AU - Zhu J AD - Harvard Reproductive Sciences Center and Reproductive Endocrine Unit (J.Z., R.E.-Y.C., L.P., C.B., S.B.S., Y.-M.C.), Massachusetts General Hospital, Boston, Massachusetts 02114; Division of Endocrinology, Department of Medicine (M.H.G., J.N.H., Y.-M.C.), Boston Children's Hospital, Boston, Massachusetts 02115; Department of Genetics (M.H.G., J.N.H.), Harvard Medical School, Boston, Massachusetts 02115; Program in Medical and Population Genetics (M.H.G., J.N.H.), Broad Institute, Cambridge, Massachusetts 02142; Division of Endocrinology and Genetics and Genome Biology Program (M.R.P.), Hospital for Sick Children, Toronto, Canada M5G 1X8; and Institute of Medical Science and Departments of Pediatrics and Physiology (M.R.P.), University of Toronto, Toronto, Canada M5S 1A8. FAU - Choa, Ruth E-Y AU - Choa RE FAU - Guo, Michael H AU - Guo MH FAU - Plummer, Lacey AU - Plummer L FAU - Buck, Cassandra AU - Buck C FAU - Palmert, Mark R AU - Palmert MR FAU - Hirschhorn, Joel N AU - Hirschhorn JN FAU - Seminara, Stephanie B AU - Seminara SB