Cleft Lip Syndrome Linked To Two Novel Genetic Mutations
Researchers hope findings will lead toward genetic testing for affected patients and families
THURSDAY, Dec. 22 (HealthDay News) -- Two novel TP63 mutations have been identified that result in the rare ankyloblepharon, ectodermal defects, and cleft lip and palate (AEC) syndrome, according to a study published in the December issue of the Archives of Dermatology.
Aimee S. Payne, M.D., Ph.D., of the University of Pennsylvania in Philadelphia, and colleagues studied two infant cases of AEC syndrome, both with skin erosion, particularly on the scalp. Histological studies showed mild basal layer vacuolization and rare dyskeratotic keratinocytes. At the blister edge, there was evidence of both acantholysis and cytolysis. Immunohistochemistry using anti-P63 monoclonal antibody showed that there was basal epidermal nuclear staining in the patients' tissue samples as well as in healthy control samples.
The researchers' DNA analysis found two novel missense mutations in the TP63 gene, resulting in L514S and R555P amino acid substitutions within the sterile alpha motif region of the p63 protein.
"The R555P mutation is the most carboxy-terminal of all the reported AEC missense mutations of p63," the authors conclude. "It is hoped that further molecular studies to elucidate the structure-function relationship of p63 and identify its downstream targets will clarify the genotype-phenotype correlation of the p63 syndromes to allow for better genetic testing and counseling of affected patients and their families."