2026-04-17T01:25:21Zhttps://recercat.cat/oai/requestoai:recercat.cat:11351/110622025-10-24T10:44:32Zcom_2072_378070com_2072_378040col_2072_378092
RECERCAT
author
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
2025-10-24T10:44:32Z
2025-10-24T10:44:32Z
2024-02-16T13:27:28Z2024-02-16T13:27:28Z2024-01-26
http://hdl.handle.net/11351/11062
Common ancestor; Hereditary leiomyomatosis; Renal cell cancerAvantpassat comú; Leiomiomatosi hereditària; Càncer de cèl·lules renalsAncestro común; Leiomiomatosis hereditaria; Cáncer de células renalesBackground
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).
Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess
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
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion