Genetic causes of familial isolated pituitary adenomas (FIPAs) remain mostly elusive. A cohort of 20 FIPA cases from 12 different geographical regions of Türkiye was included to characterize clinical and genetic features. Whole exome sequencing (WES) was performed on genomic DNA of index cases, followed by confirmation through Sanger sequencing utilizing indexes and their relatives to interpret disease associated variants. Index cases among homogeneous (n = 10) and heterogeneous (n = 10) FIPA groups (45% female /55% male), age at diagnosis was 36.3 ± 11.98 years, median follow-up was 103 months. GH-secreting adenomas dominated homogeneous group (60% vs. 30% of heterogeneous group). Two predefined AIP variants [p.(Arg304Ter) and p.(Arg81Ter)] and a novel AIP variant at splice acceptor site [(c.646-1G > C)] were detected in three families (15%). Syndromic heterozygous novel NF1 [p.(Thr1295Ala)], TSC1 [p.(Arg517Gln)], SDHB [p.(Glu176Gly)] and CDH23 [p.(Ala765Val)] variants were detected in four FIPA families, along with novel candidate genes in the remaining patients of the cohort. Among all detected variants, three [p.(Arg81Ter) and (c.646-1G > C) in AIP, and p.(Glu216GlysfsTer61) in TINF2] were classified as pathogenic according to ACMG. AIP mutation frequency was 15% in our cohort. A novel AIP variant, and novel variations in syndromic genes were identified, along with the introduction of candidate genes. WES method is a crucial approach to identify new rare genetic variants in familial settings, and it will pave the way for future studies on targeted therapies.
Keywords: AIP; FIPAs; Novel variants; Syndromic genes; Whole exome sequencing.
© 2025. The Author(s).