RT Journal Article
T1 Molecular analysis of the APC and MUTYH genes in Galician and Catalonian FAP families: a different spectrum of mutations?
A1 Gómez Fernández, Nuria
A1 Castellví Bel, Sergi
A1 Fernández Rozadilla, Ceres
A1 Balaguer, Francesc
A1 Muñoz, Jenifer
A1 Madrigal, Irene
A1 Milà, Montserrat
A1 Graña Suárez, Begoña
A1 Vega Gliemmo, Ana Paula
A1 Castells, Antoni
A1 Carracedo Álvarez, Ángel
A1 Ruiz Ponte, Clara
AB Background: Familial adenomatous polyposis (FAP) is an autosomal dominant-inheritedcolorectal cancer syndrome, caused by germline mutations in the APC gene. Recently, biallelicmutations in MUTYH have also been identified in patients with multiple colorectal adenomas and inAPC-negative patients with FAP. The aim of this work is therefore to determine the frequency ofAPC and MUTYH mutations among FAP families from two Spanish populations.Methods: Eighty-two unrelated patients with classical or attenuated FAP were screened for APCgermline mutations. MUTYH analysis was then conducted in those APC-negative families and in 9additional patients from a previous study. Direct sequencing, SSCP analysis and TaqMan genotypingwere used to identify point and frameshift mutations, meanwhile large rearrangements in the APCgene were screened by multiplex ligation-dependent probe amplification (MLPA).Results: APC germline mutations were found in 39% of the patients and, despite the great numberof genetic variants described so far in this gene, seven new mutations were identified. The twohotspots at codons 1061 and 1309 of the APC gene accounted for 9,4% of the APC-positive families,although they were underrepresented in Galician samples. The deletion at codon 1061 was notfound in 19 APC-positive Galician patients but represented 23% of the Catalonian positive families(p = 0,058). The same trend was observed at codon 1309, even though statistical analysis showedno significance between populations. Twenty-four percent of the APC-negative patients carriedbiallelic MUTYH germline mutations, and showed an attenuated polyposis phenotype generallywithout extracolonic manifestations. New genetic variants were found, as well as the two hotspotsalready reported (p.Tyr165Cys and p.Gly382Asp).
PB BMC
SN 1471-2350
YR 2009
FD 2009
LK http://hdl.handle.net/10347/22767
UL http://hdl.handle.net/10347/22767
LA eng
NO Gómez-Fernández, N., Castellví-Bel, S., Fernández-Rozadilla, C. et al. Molecular analysis of the APC and MUTYH genes in Galician and Catalonian FAP families: a different spectrum of mutations?. BMC Med Genet 10, 57 (2009). https://doi.org/10.1186/1471-2350-10-57
NO This work was supported by grants from the Fondo de Investigación Sanitaria (FIS 05/2031, 04/1126, 05/0071, 08/0025, 08/1276), Xunta de Galicia(PGIDIT07PXIB9101209PR), Fundación de Investigación Médica MutuaMadrileña (to CRP, SCB and BG), Ministerio de Educación y Ciencia (SAF07-64873), Asociación Española contra el Cáncer, Fundación Olga Torres(SCB), Acción Transversal contra el Cáncer (Instituto de Salud Carlos III)and Axudas para a intensificación da actividade investigadora dos profesionais dos centros do sistema sanitario público de Galicia RHI07/04 (Consellería de Sanidade, Xunta de Galicia) to CRP. CIBERER and CIBEREHD arefunded by the Instituto de Salud Carlos III. NGF is supported by a MariaBarbeito's Fellowship from Xunta de Galicia, SCB is supported by a contract from the Fondo de Investigación Sanitaria (CP 03-0070, Ministerio deSanidad), CF has obtained a FPU' Fellowship from the Ministerio de Educacion, FB received a research grant from Fundacion Caja Madrid, and IM issupported by a contract from the CIBERER
DS Minerva
RD 26 abr 2026