Novel Phenotype And Mutation Study Of HOXD13Gene In A Congential Synpolydactyly Pedigree Of Chinese

Background and Purpose:Congenital syndactyly(SPD) is a common autosomal dominantdisease,Which typical is characterized by syndactyly between the third andfourth fingers and between the fourth and fifth toes, with a partial or completeextra digit in the syndactylous web. Incomplete penetrance and variableexpressivity both between and within affected families are common. It isrecognized that the HOXD13gene were be an imporyant candidate genes causecongenital synpolydactyly. In humans, HOX genes are thought to encode ahighly conserved family of transcription factors, which plays an important rolein embryonic development. HOX gene clusters located in7、17、12、2chromosome areas. HOXD13gene locate in5’end of chromosome2. TheHOXD13gene contains two exons. Exon1region easily lead to polyalaninechain to extend the mutation, The Exon2region easily lead to base deletionand missense mutations, nonsense mutations. EPHA7is the downstream geneof HOXD13regulated, which widely expressed in embryonic tissues,regulating the development of the nervous system, tissue differentiation andother aspects. HOXD13gene regulate transcriptional expression of EPHA7gene through combination of the promoter.In this article, we carry out clinical phenotypes exploration and moleculargenetics of a Congential Synpolydactyly Pedigree Of Chinese.To furtherclarify the types of congenital syndactyly. Analysis may result in abnormaldeformity causes and mechanisms, explore the molecular mechanisms ofdisease genes role.Subjects and methods: To survey a congential synpolydactyly Pedigree of China’s Jilin Province,summary of the clinical phenotype of patients with their families, to draw thepedigree analysis of genetic characteristics, while collect the blood samples offamily members, extracted from peripheral blood DNA, design HOXD13exonprimers, PCR amplification of the target gene, the amplified products by directsequencing and analysis of whether the mutation. At the same time, the use ofthe luciferase reporter gene on the newly discovered mutations in the gene forfurther functional experiments.Result:According analysts Pedigree, the patient is consistent with autosomaldominant inheritance. Summarize the clinical manifestations of the Departmentof patients, in line with the congenital synpolydactyly features. HOXD13geneexon2region found a new missense mutation: c893G> A (p.R298Q),893bases from guanine by molecular genetic studies, were found in all patients.Inthe pedigree (G) mutation changed from CGG to CAG, resulting in arginineglutamine substitution for the adenine (A),298amino acids (the homeodomainarea31) of the HOXD13gene. The same gene mutation found in the case offamilies of clinically normal patients, which is Stealth carrier, suggesting thatthe penetrance insufficiency of the family. Mutant, the dual-luciferase reportergene function test results showed that contrast to wild-type HOXD13gene, themutant HOXD13(R31Q) significantly reduced transcriptional activity of thedownstream EPHA7gene promoter.Conclusion:1. The pedigree shows the penetrance incomplete and refers to theabnormal performance diversify and enrich the clinical phenotype of SPD.2. HOXD13gene in exon2of the pedigree of the newly discoveredmissense mutation, resulting in amino acid changes, thus affecting theHOXD13DNA binding caused by HOXD13diminished binding capacity of the downstream gene transcription, speculated that the mutation may havecontributed to and refers to multi-fingered one of the deformity of themolecular mechanisms.