TP63 Gene Mutations in Chinese P63 Syndrome Patients

• DOI: 10.1177/0022034510366804
• Publication Date: 2010-04-22T02:34:41Z
• Authors: W. Yin; X. Ye; L. Shi; Q.K. Wang; H. Jin; P. Wang; Z. Bian
• Keywords: Male; 0301 basic medicine; China; Adolescent; Models, Genetic; Cleft Lip; DNA Mutational Analysis; Limb Deformities, Congenital; Mutation, Missense; Syndrome; Pedigree; Protein Structure, Tertiary; 3. Good health; Cleft Palate; 03 medical and health sciences; Asian People; Ectodermal Dysplasia; Ectoderm; Trans-Activators; Humans; Female; Breast; Anodontia

TP63 plays an essential role in the development of epidermis and skin appendages. Mutations in TP63 can give rise to a series of syndromes characterized by various combinations of ectodermal dysplasia, limb malformations, and orofacial clefting in many populations. To test whether TP63 is the disease-causative gene for these phenotypes in Chinese, we recruited two Chinese Ectrodactyly-Ectodermal-dysplasia-Cleft lip/palate syndrome (EEC) cases and a Limb-Mammary-Syndrome (LMS) patient to carry out TP63 gene sequencing. Three missense mutation, c.812G>C (Ser271Thr), c.611G>A (Arg204Gln), and c.680G>A (Arg227Gln), which lead to the substitution of highly conserved amino acids in the DNA-binding domain of TP63, were identified. These mutations were predicted to disrupt DNA-binding specificity and affinity. To our knowledge, this is the first report of EEC and LMS syndromes in individuals of Chinese descent. Analysis of our data demonstrated that TP63 is critical for the development of ectoderm in humans.