New Findings in Oligogenic Inheritance of Congenital Hypogonadotropic Hypogonadism

Overview

Journal Arch Med Sci

Specialty General Medicine

Date 2022 Mar 23

PMID 35316923

Authors

Agnieszka Gach

Iwona Pinkier

Urszula Wysocka

Kinga Salacinska

Dominik Salachna

Maria Szarras-Czapnik

Aleksandra Pietrzyk

Agata Sakowicz

Anna Nykel

Lena Rutkowska

Magda Rybak-Krzyszkowska

Magda Socha

Aleksander Jamsheer

Lucjusz Jakubowski

Affiliations

Soon will be listed here.

Abstract

Introduction: Congenital hypogonadotropic hypogonadism results from a dysfunction of the hypothalamic-pituitary-gonadal axis, which is essential for the development and function of the reproductive system. It may be associated with anosmia, referred to as Kallmann syndrome, or a normal sense of smell. Numerous studies have proven that hypogonadotropic hypogonadism is not simply a monogenic Mendelian disease, but that more than one gene may be involved in its pathogenesis in a single patient. The oligogenic complex architecture underlying the disease is still largely unknown.

Material And Methods: Targeted next-generation sequencing (NGS) was used to screen for DNA variants in a cohort of 47 patients with congenital hypogonadotropic hypogonadism. The NGS panel consists of over 50 well-known and candidate genes, associated with hypogonadotropic state.

Results: Here we report the identification of new oligogenic variants in , and These genes are known to contribute to the phenotype of hypogonadotropic hypogonadism, yet our results point to potential new "partners" underlying digenic and trigenic patterns.

Conclusions: The finding supports the importance of oligogenic inheritance and demonstrates the complexity of genetic architecture in hypogonadotropic hypogonadism. It also underlines the necessity for developing fine-tuned guidelines to provide a tool for adequate and precise sequence variant classification in non-Mendelian conditions.

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