Mutation Analysis Of P63 Gene In The First Chinese Family With Adult Syndrome

IntroductionADULT syndrome (acro-dermato-ungual-lacrimal-tooth syndrome, OMIM 103285) is a typical ectodermal dysplasia syndrome affecting multiple organs. p63 gene, the causative gene for this disorder, plays a crucial role in embryonic development, especially in the morphogenesis of limbs and other ectodermal-derived tissues.The p63 gene is highly expressed in the nuclei of basal cells of the skin, cervix, tongue, esophagus, mammary glands, prostate, and urothelium. It plays a crucial role in the development of the epidermis and embryonic appendages. Complete abrogation of p63 gene function in an animal model revealed the relevance of p63 gene to the normal development of ectodermally derived tissues. The p63 gene knock-out mouse showed truncation of the limbs, as well as absence of epidermis, prostate, breast and urothelial tissues, reflecting loss of ectodermal stem cell.Nowdays, only a few ADULT syndrome has been reported in the world. It is low incidence, and possesses variable clinical behaviors and mutation sites, leading to difficulty in the diagnosis of this disease. Moreover, recent studies have linked p63 mutation to the development of disease. However, the genetic characteristics of ADULT syndrome are still not well known. The further study of the genetics of this disorder contributes to its diagnosis, prevention and treatment. .ObjectiveTo definite the mutation site of p63 gene in the first family with ADULT syndrom and investige mutation of p63 gene and the relationship between the ADULT syndrome. It is important to Clinical genetic diagnosis and treatment of this disease.MethodsMutation analysis of p63 gene in the first family was performed using direct DNA sequencing.ResultsThe sequence analysis of exon 8 of p63 gene disclosed a heterozygous G>A substitution at nucleotide 893 (R298Q) in the proband. In addition, a single nucleotide polymorphism (SNP) rs16864880 in the downstream flanking region (DFR) of p63 exon 8 was also identified in this family. The proband and the paternal side including her father exhibited the C/G genotype at this position. The C/G variant frequency in the paternal was significantly higher as compared with the maternal (6/10 vs 0/6, P=0.034).ConclusionsA heterozygous mutation of R298Q in exon 8 of p63 gene revealed in the first case of Chinese ADULT syndrome. ADULT syndrome may be caused by the p63 gene mutation, and it might have closer genetic association with the paternal side in this family.