title: Isolated ectrodactyly caused by a heterozygous missense mutation in the transactivation domain of TP63.
abstract: We report a Mexican boy with isolated ectrodactyly (split hand malformation) in whom a new mutation was identified in exon 3 of the TP63 gene. In contrast to previously reported patients with isolated split hand/foot anomaly and mutations in the DNA binding domain of Tp63, the mutation described herein induce an amino acid substitution (R97C) in the canonical transactivation (TA) domain. To our knowledge, this is the first naturally occurring mutation described so far in this part of the protein. Based on the genotype-phenotype correlation observed in our patient, we hypothesize that integrity of the TA domain of Tp63 is critical for normal limb development.
authors.affiliation: Department of Genetics, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico. jczenteno@salud.gob.mx
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Zenteno
authors.forename: Valeria
authors.initials: V
authors.lastname: Berdón-Zapata
authors.forename: Susana
authors.initials: S
authors.lastname: Kofman-Alfaro
authors.forename: Osvaldo M
authors.initials: OM
authors.lastname: Mutchinick
mesh_terms: D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins; D016147:Genes, Tumor Suppressor; D006228:Hand Deformities, Congenital / Q000235:genetics* / Q000473:pathology; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D020125:Mutation, Missense; D010750:Phosphoproteins / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors; D015533:Transcriptional Activation / Q000235:genetics; D025521:Tumor Suppressor Proteins
chemical_list: D004268:DNA-Binding Proteins; D010750:Phosphoproteins; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D004247:DNA