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Title: | Genetic and clinical characterization of a novel FH founder mutation in families with hereditary leiomyomatosis and renal cell cancer syndrome |
Author: | Sánchez Heras, Ana Beatriz Dámaso, Estela Castillejo, Adela Robledo, Mercedes Teulé, Alexandre Lázaro García, Conxi Sánchez Martínez, Rosario Zúñiga, Ángel López Fernández, Adrià Balmaña, Judith Robles, Luis Ramon y Cajal, Teresa Castillejo, M. Isabel Ibañez, Raquel Perea Sevila, Carmen Martínez Sánchez Mira, Andrea Escandell, Inés Gómez, Luís Berbel, Pere Soto, José Luis |
Keywords: | Mutació (Biologia) Càncer de ronyó Malalties hereditàries Mutation (Biology) Renal cancer Genetic diseases |
Issue Date: | 26-Jan-2024 |
Publisher: | Springer Science and Business Media LLC |
Abstract: | 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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1186/s13023-024-03017-z |
It is part of: | Orphanet Journal of Rare Diseases, 2024, vol. 19, num. 1 |
URI: | http://hdl.handle.net/2445/207940 |
Related resource: | https://doi.org/10.1186/s13023-024-03017-z |
ISSN: | 1750-1172 |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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