In:
Hormone Research in Paediatrics, S. Karger AG, Vol. 95, No. 4 ( 2022), p. 384-392
Abstract:
〈 b 〉 〈 i 〉 Introduction: 〈 /i 〉 〈 /b 〉 Idiopathic hypogonadotropic hypogonadism (IHH) is a rare reproductive disorder resulting from gonadotropin-releasing hormone (GnRH) deficiency. However, in only approximately half of patients with IHH is it possible to identify a likely molecular diagnosis. Mice lacking Slit2 have a reduced number or altered patterning of GnRH neurons in the brain. In order to assess the contribution of 〈 i 〉 SLIT2 〈 /i 〉 to IHH, we carried out a candidate gene burden test analysis. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 A total of 196 IHH probands and 2,362 ethic-matched controls were recruited for this study. The IHH probands and controls were subjected to whole-exome sequencing. In the IHH patients with 〈 i 〉 SLIT2 〈 /i 〉 variants and their available family members, detailed phenotyping and segregation analysis were performed. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Nine heterozygous 〈 i 〉 SLIT2 〈 /i 〉 rare sequencing variants (RSVs) were identified in 13 probands, with a prevalence of 6.6%. Furthermore, we identified an increased mutational burden for 〈 i 〉 SLIT2 〈 /i 〉 in this cohort (odds ratio = 2.2, 〈 i 〉 p 〈 /i 〉 = 0.021). The segregation analysis of available IHH families revealed that the majority of 〈 i 〉 SLIT2 〈 /i 〉 RSVs were inherited from unaffected or partially affected parents. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 Our study suggests 〈 i 〉 SLIT2 〈 /i 〉 as a new IHH-associated gene and expands the clinical and genetic spectrum of IHH. Furthermore, 〈 i 〉 SLIT2 〈 /i 〉 alone does not appear to be sufficient to cause the disorder, and it may interact with other IHH-associated genes to induce a clinical phenotype.
Type of Medium:
Online Resource
ISSN:
1663-2818
,
1663-2826
Language:
English
Publisher:
S. Karger AG
Publication Date:
2022
detail.hit.zdb_id:
2540224-9
