Jankowska Katarzyna K, Kutkowska-Kazmierczak Anna, Ślusarczyk Klaudia, Domaszewicz Alicja, Duk Katarzyna, Wolski Jan Karol, Kozioł Katarzyna, Sawicka Justyna, Klapecki Jakub, Laudański Piotr, Wertheim-Tysarowska Katarzyna, Rygiel Agnieszka Magdalena
Department of Endocrinology, Center of Postgraduate Medical Education, Bielanski Hospital, Warsaw, Poland.
Department of Medical Genetics, Institute of Mother and Child, Warsaw, Poland.
J Appl Genet. 2025 Jan 15. doi: 10.1007/s13353-024-00935-3.
Recently, the knowledge of the genetic basis of fertility disorders has expanded enormously, mainly thanks to the use of next-generation sequencing (NGS). However, the genetic cause of infertility, in the majority of patients, is still undefined. The aim was to identify novel and recurrent pathogenic/likely pathogenic variants in patients with isolated infertility or puberty delay using a targeted NGS technique. We have enrolled 41 patients (36 males and 5 females) with infertility problems or delayed puberty. We included the patients with hypogonadotropic hypogonadism (n = 12), hypergonadotropic hypogonadism (n = 15), abnormal sperm parameters (n = 10), androgen insensitivity syndrome (n = 3) and 46,XY gonadal dysgenesis (n = 1). Genetic tests were performed using targeted NGS panel of 35 genes implicated in fertility. Pathogenic or likely pathogenic variants potentially explaining the clinical phenotype were identified in 12 of 41 patients (29%). These included 9 of 12 patients (75%) with hypogonadotropic hypogonadism, 2 of 3 patients (66%) with androgen insensitivity syndrome, and the single patient with 46,XY gonadal dysgenesis. Among the 18 identified variants, 4 were novel (FGF8:p.Ala147Thr; SEMA3A:p.Arg544Cys; FGFR1:p.Thr141IlefsTer10; NSMF: p.Tyr242Cys), while 14 were recurrent. Our study expands the knowledge of the genetic basis of the infertility disorders and highlights the importance of genetic testing for proper diagnosis making and genetic counselling.
最近，主要得益于新一代测序（NGS）技术的应用，关于生育障碍遗传基础的知识有了极大的扩展。然而，在大多数患者中，不孕的遗传原因仍不明确。本研究旨在使用靶向NGS技术，在孤立性不孕或青春期延迟的患者中鉴定新的和复发性的致病/可能致病变异。我们招募了41例有不孕问题或青春期延迟的患者（36例男性和5例女性）。我们纳入了低促性腺激素性性腺功能减退患者（n = 12）、高促性腺激素性性腺功能减退患者（n = 15）、精子参数异常患者（n = 10）、雄激素不敏感综合征患者（n = 3）和46,XY性腺发育不全患者（n = 1）。使用包含35个与生育相关基因的靶向NGS panel进行基因检测。在41例患者中的12例（29%）中鉴定出了可能解释临床表型的致病或可能致病变异。这些包括12例低促性腺激素性性腺功能减退患者中的9例（75%）、3例雄激素不敏感综合征患者中的2例（66%）以及唯一的1例46,XY性腺发育不全患者。在鉴定出的18个变异中，4个是新的（FGF8:p.Ala147Thr；SEMA3A:p.Arg544Cys；FGFR1:p.Thr141IlefsTer10；NSMF:p.Tyr242Cys），而14个是复发性的。我们的研究扩展了对不孕疾病遗传基础的认识，并强调了基因检测对于正确诊断和遗传咨询的重要性。
