CLINICAL RESEARCH
New findings in oligogenic inheritance of congenital hypogonadotropic hypogonadism
 
More details
Hide details
1
Department of Genetics, Polish Mother’s Memorial Hospital Research Institute, Lodz, Poland
2
Department of Endocrinology and Diabetology, Children’s Memorial Health Institute, Warsaw, Poland
3
Department of Genetics and Pathomorphology, Faculty of Medicine and Health Sciences, University of Zielona Gora, Poland
4
Department of Medical Biotechnology, Medical University of Lodz, Lodz, Poland
5
Department of Obstetrics and Perinatology, University Hospital in Krakow, Krakow, Poland
6
Department of Medical Genetics, Poznan University of Medical Sciences, Poznan, Poland
Submission date: 2020-06-27
Final revision date: 2020-08-11
Acceptance date: 2020-08-11
Online publication date: 2020-09-18
 
 
KEYWORDS
TOPICS
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 SPRY4/SEMA3A, SRA1/SEMA7A, CHD7/SEMA7A, CCDC141/POLR3B/POLR3B, and PROKR2/SPRY4/NSMF. 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.

eISSN:1896-9151
ISSN:1734-1922