New findings in oligogenic inheritance of congenital hypogonadotropic hypogonadism.
| Autor: | Gach A; Department of Genetics, Polish Mother's Memorial Hospital Research Institute, Lodz, Poland., Pinkier I; Department of Genetics, Polish Mother's Memorial Hospital Research Institute, Lodz, Poland., Wysocka U; Department of Genetics, Polish Mother's Memorial Hospital Research Institute, Lodz, Poland., Sałacińska K; Department of Genetics, Polish Mother's Memorial Hospital Research Institute, Lodz, Poland., Salachna D; Department of Genetics, Polish Mother's Memorial Hospital Research Institute, Lodz, Poland., Szarras-Czapnik M; Department of Endocrinology and Diabetology, Children's Memorial Health Institute, Warsaw, Poland., Pietrzyk A; Department of Genetics and Pathomorphology, Faculty of Medicine and Health Sciences, University of Zielona Gora, Poland., Sakowicz A; Department of Medical Biotechnology, Medical University of Lodz, Lodz, Poland., Nykel A; Department of Genetics, Polish Mother's Memorial Hospital Research Institute, Lodz, Poland., Rutkowska L; Department of Genetics, Polish Mother's Memorial Hospital Research Institute, Lodz, Poland., Rybak-Krzyszkowska M; Department of Obstetrics and Perinatology, University Hospital in Krakow, Krakow, Poland., Socha M; Department of Medical Genetics, Poznan University of Medical Sciences, Poznan, Poland., Jamsheer A; Department of Medical Genetics, Poznan University of Medical Sciences, Poznan, Poland., Jakubowski L; Department of Genetics, Polish Mother's Memorial Hospital Research Institute, Lodz, Poland. |
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| Jazyk: | angličtina |
| Zdroj: | Archives of medical science : AMS [Arch Med Sci] 2020 Sep 18; Vol. 18 (2), pp. 353-364. Date of Electronic Publication: 2020 Sep 18 (Print Publication: 2022). |
| DOI: | 10.5114/aoms.2020.98909 |
| Abstrakt: | 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. Competing Interests: The authors declare no conflict of interest. (Copyright: © 2020 Termedia & Banach.) |
| Databáze: | MEDLINE |
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