1Valeria Berdón-Zapata, 1M Granillo-Alvarez, 2M Valdés-Flores, 3JE García-Ortíz, 1S Kofman-Alfaro, 1JC Zenteno-Ruiz
1Department of Genetics, Hospital General de México-Fac.Medicina, UNAM, Dr.Balmis 148, Col. Doctores, 06726, México D.F., México, 2Department of Genetics, Instituto Nacional de Rehabilitación, Calz. México Xochimilco, México D.F., México, 3Department of Immunobiology, Centro de Investigación Biomédica, UAdeC, Torreón, Coahuila, México
Ectrodactyly is a common congenital limb malformation that involves a central reduction defect of the hands and/or feet which is frequently associated with other phenotypic abnormalities. The condition appears to be genetically heterogeneous and recently it has been demonstrated that mutations in the p63 gene, a homologue of the tumor suppressor gene p53, are the cause of at least five autosomal dominant genetic syndromes which feature ectrodactyly: EEC (ectrodactyly, ectodermal dysplasia, and facial clefting), SHFM (split-hand/split-foot malformation), LMS (limb-mammary syndrome), ADULT (acro-dermato-ungual-lacrimal-tooth syndrome), and isolated SHFM (split hand-split foot malformation). In this study, we performed genetic analysis of the p63 gene in a group of 13 patients with ectrodactyly (syndromic and isolated). Four patients with syndromic ectrodactyly had p63 heterozygous point mutations that affect the DNA binding domain of the protein. In a patient with diagnosis of EEC syndrome, we found a CGC to CAC mutation in exon 7 which predicted an arginine to hystidine change at position 279 of the p63 protein (R279H) which is located in the DNA binding domain of p63; in other two patients (a mother with EE syndrome and her daughter with EEC syndrome), a change from CGG to TGG at codon 204 in exon 5 predicted a shift from arginine to tryptophan (R204W), also situated in the DNA binding domain of the protein; a third mutation was identified in another EE syndrome patient, and was identical to that described in the first subject (R279H). We discuss on the clinical features of these subjects and also on the phenotype-genotype correlation observed in this and previous studies.
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