Heterozygous Germline Mutations in the p53 Homolog p63 Are the Cause of EEC Syndrome
Copyright policy )Heterozygous Germline Mutations in the p53 Homolog p63 Are the Cause of EEC Syndrome
EEC syndrome is an autosomal dominant disorder characterized by ectrodactyly, ectodermal dysplasia, and facial clefts. We have mapped the genetic defect in several EEC syndrome families to a region of chromosome 3q27 previously implicated in the EEC-like disorder, limb mammary syndrome (LMS). Analysis of the p63 gene, a homolog of p53 located in the critical LMS/EEC interval, revealed heterozygous mutations in nine unrelated EEC families. Eight mutations result in amino acid substitutions that are predicted to abolish the DNA binding capacity of p63. The ninth is a frameshift mutation that affects the p63alpha, but not p63beta and p63gamma isotypes. Transactivation studies with these mutant p63 isotypes provide a molecular explanation for the dominant character of p63 mutations in EEC syndrome.
- Harvard University United States
- Queensland University of Technology Australia
- Royal Hospital for Children United Kingdom
- Leiden University Netherlands
- Leeds Teaching Hospitals NHS Trust United Kingdom
EXPRESSION, Genetic Markers, Male, Models, Molecular, LIMB DEVELOPMENT, Foot Deformities, Congenital, DATABASE, Molecular Sequence Data, PROTEIN, Expression, SPLIT FOOT LOCUS, Gene, SEQUENCE, Database, Ectodermal Dysplasia, Complex, Sequence, Humans, Abnormalities, Multiple, Genes, Tumor Suppressor, Amino Acid Sequence, Limb development, Germ-Line Mutation, COMPLEX, Biochemistry, Genetics and Molecular Biology(all), Protein, Chromosome Mapping, Membrane Proteins, DEFECTS, Genes, p53, GENE, MODEL, DNA-Binding Proteins, Split foot locus, Amino Acid Substitution, Face, Defects, Female, Chromosomes, Human, Pair 3, Hand Deformities, Congenital, Model
EXPRESSION, Genetic Markers, Male, Models, Molecular, LIMB DEVELOPMENT, Foot Deformities, Congenital, DATABASE, Molecular Sequence Data, PROTEIN, Expression, SPLIT FOOT LOCUS, Gene, SEQUENCE, Database, Ectodermal Dysplasia, Complex, Sequence, Humans, Abnormalities, Multiple, Genes, Tumor Suppressor, Amino Acid Sequence, Limb development, Germ-Line Mutation, COMPLEX, Biochemistry, Genetics and Molecular Biology(all), Protein, Chromosome Mapping, Membrane Proteins, DEFECTS, Genes, p53, GENE, MODEL, DNA-Binding Proteins, Split foot locus, Amino Acid Substitution, Face, Defects, Female, Chromosomes, Human, Pair 3, Hand Deformities, Congenital, Model
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