2026-04-17T06:06:04Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/110622025-10-24T10:44:32Zcom_2072_378070com_2072_378040col_2072_378092

00925njm 22002777a 4500 dc Dámaso, Estela author Castillejo Castillo, Adela author Robledo, Mercedes author Teule, Alex author LAZARO GARCIA, CONXI author Lopez-Fernandez, Adrià author Sanchez-Heras, Ana Beatriz author Balmaña, Judith author 2024-02-16T13:27:28Z 2024-02-16T13:27:28Z 2024-01-26 Common ancestor; Hereditary leiomyomatosis; Renal cell cancer Avantpassat comú; Leiomiomatosi hereditària; Càncer de cèl·lules renals Ancestro común; Leiomiomatosis hereditaria; Cáncer de células renales Background Hereditary leiomyomatosis and renal cell cancer syndrome is a rare autosomal dominant hereditary syndrome. Previously, we published the largest cohort of FH mutation carriers in Spain and observed a highly recurrent missense heterozygous variant, FH(NM_000143.4):c.1118A > G p.(Asn373Ser), in 104 individuals from 31 apparently unrelated families. Here, we aimed to establish its founder effect and characterize the associated clinical phenotype. Results Haplotype analysis confirmed that families shared a common haplotype (32/38 markers) spanning 0.61–0.82 Mb, indicating this recurrent variant was inherited from a founder ancestor. Cutaneous and uterine leiomyomatosis were diagnosed in 64.6% (64/99) and 98% (50/51) of patients, respectively, and renal cell cancer was present in 10.4% (10/96). The pathogenic FH_c.1118A > G variant is a Spanish founder mutation that originated 12–26 generations ago. We estimate that the variant may have appeared between 1370 and 1720. Individuals carrying this founder mutation had similar frequency of renal cell cancer and a higher frequency of renal cysts and leiomyomas than those in other cohorts of this syndrome. Conclusions In the Spanish province of Alicante there is a high prevalence of HLRCC because of the founder mutation FH c.1118A > G; p.(Asn373Ser). The characterization of founder mutations provides accurate and specific information regarding their penetrance and expressivity. In individuals with suspected HLRCC from the province of Alicante, genetic testing by direct analysis of the founder FH c.1118A > G; p.(Asn373Ser) mutation may be a faster and more efficient diagnostic tool compared with complete gene sequencing. Project founded by Spanish Society of Medical Oncology Foundation (FSEOM). SEOM + 1 Grant (UGP-19-428). http://hdl.handle.net/11351/11062 Anomalies cromosòmiques Músculs - Càncer - Aspectes genètics Ronyons - Càncer - Aspectes genètics Malalties congènites DISEASES::Neoplasms::Neoplastic Syndromes, Hereditary DISEASES::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Connective and Soft Tissue::Neoplasms, Muscle Tissue::Leiomyoma::Leiomyomatosis DISEASES::Neoplasms::Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Urologic Neoplasms::Kidney Neoplasms::Carcinoma, Renal Cell PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::Mutation ENFERMEDADES::neoplasias::síndromes neoplásicos hereditarios ENFERMEDADES::neoplasias::neoplasias por tipo histológico::neoplasias de tejido conjuntivo y de tejidos blandos::neoplasias de tejido muscular::leiomioma::leiomiomatosis ENFERMEDADES::neoplasias::neoplasias::neoplasias por localización::neoplasias urogenitales::neoplasias urológicas::neoplasias renales::carcinoma de células renales FENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::mutación Genetic and clinical characterization of a novel FH founder mutation in families with hereditary leiomyomatosis and renal cell cancer syndrome