Family-based genome-wide association study in Patagonia confirms the association of the DMD locus and cleft lip and palate

The etiology of cleft lip with or without cleft palate (CL±P) is complex and heterogeneous, and multiple genetic and environmental factors are involved. Some candidate genes reported to be associated with oral clefts are located on the X chromosome. At least three genes causing X‐linked syndromes [midline 1 (MID1), oral‐facial‐digital syndrome 1 (OFD1), and dystrophin (DMD)] were previously found to be associated with isolated CL±P. We attempted to confirm the role of X‐linked genes in the etiology of isolated CL±P in a South American population through a family‐based genome‐wide scan. We studied 27 affected children and their mothers, from 26 families, in a Patagonian population with a high prevalence of CL±P. We conducted an exploratory analysis of the X chromosome to identify candidate regions associated with CL±P. Four genomic segments were identified, two of which showed a statistically significant association with CL±P. One is an 11‐kb region of Xp21.1 containing the DMD gene, and the other is an intergenic region (8.7 kb; Xp11.4). Our results are consistent with recent data on the involvement of the DMD gene in the etiology of CL±P. The MID1 and OFD1 genes were not included in the four potential CL±P‐associated X‐chromosome genomic segments. Fil: Fonseca, Renata F.. Universidade Federal do Rio de Janeiro; Brasil. National Institute of Population Medical Genetics; Brasil Fil: de Carvalho, Flávia M.. Universidade Federal do Rio de Janeiro; Brasil. National Institute of Population Medical Genetics; Brasil. Instituto Oswaldo Cruz; Brasil Fil: Poletta, Fernando Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET.; Argentina. National Institute of Population Medical Genetics; Brasil. Instituto Oswaldo Cruz; Brasil Fil: Montaner, David. Centro de Investigación Biomédica en Red de Enfermedades Raras; España. Centro de Investigaciones Príncipe Felipe; España Fil: Dopazo, Joaquin. Centro de Investigación Biomédica en Red de Enfermedades Raras; España. Centro de Investigaciones Príncipe Felipe; España Fil: Mereb, Juan C.. Provincia de Río Negro. Ministerio de Salud. Hospital De Área El Bolsón; Argentina Fil: Moreira, Miguel A. M.. National Cancer Institute; Brasil Fil: Seuanez, Hector N.. National Cancer Institute; Brasil. Universidade Federal do Rio de Janeiro; Brasil Fil: Vieira, Alexandre R.. University of Pittsburgh; Estados Unidos Fil: Castilla, Eduardo Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET.; Argentina. National Institute of Population Medical Genetics; Brasil. Instituto Oswaldo Cruz; Brasil Fil: Orioli, Iêda M.. Universidade Federal do Rio de Janeiro; Brasil. National Institute of Population Medical Genetics; Brasil