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. 2023 Sep 29:16:4429-4439.
doi: 10.2147/IJGM.S430904. eCollection 2023.

Clinical Manifestations, Genetic Variants and Therapeutic Evaluation in Sporadic Chinese Patients with Idiopathic Hypogonadotropic Hypogonadism

Dongye He #  1   2 , Hailing Sun  1 , Mei Zhang  1   3 , Yanying Li  1   3 , Fupeng Liu  1   2 , Yanhong Zhang  1   3 , Mingming He  1 , Bo Ban #  1   2   3
Affiliations

Clinical Manifestations, Genetic Variants and Therapeutic Evaluation in Sporadic Chinese Patients with Idiopathic Hypogonadotropic Hypogonadism

Dongye He et al. Int J Gen Med. .

Abstract

Purpose: Genetic factors account for a large proportion of idiopathic hypogonadotropic hypogonadism (IHH) etiologies, although not necessarily a complete genetic basis. This study aimed to characterize the clinical presentations, genetic variants, and therapeutic outcomes of patients with sporadic IHH, which may be helpful for genetic counseling and treatment decisions.

Patients and methods: Eleven Chinese patients with IHH were retrospectively analyzed. Rare genetic variants were evaluated using whole-exome sequencing and bioinformatics analysis and were further classified according to the ACMG-AMP guidelines. The therapeutic responses of patients were further evaluated.

Results: Six heterozygous variants of SOX10, WDR11, PROKR2, CHD7 and FGF17 were detected in five Kallmann syndrome (KS) patients, whereas two heterozygous variants of CHD7 and PROKR2 were detected in two normosmic IHH (nIHH) patients. Among these variants, a novel likely pathogenic variant in the SOX10 (c.429-1G>C) was considered to cause the KS phenotype in patient 02, and two potential variants of uncertain significance (VUS) in CHD7 (c.3344G>A and c.7391A>G) possibly contributed to the KS phenotype in patient 05 and the nIHH phenotype in patient 07, which need to be confirmed by further evidence. Additionally, long-term testosterone or estradiol replacement treatment effectively improved the development of sexual characteristics in patients with IHH.

Conclusion: Next-generation sequencing is a powerful tool for identifying the molecular etiology and early diagnosis of IHH. Efficient therapeutic outcomes strongly indicate a need for timely treatment.

Keywords: Kallmann syndrome; follicle-stimulating hormone; genetic variant; hormone treatment; luteinizing hormone; normosmic idiopathic hypogonadotropic hypogonadism.

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Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Pedigree chart and genetic variants identified in patients affected with IHH.
Figure 2
Figure 2
Changes in testosterone, estradiol, LH and FSH levels of patients affected with IHH during therapy.
See this image and copyright information in PMC

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