Clinical And Genetic Studies Of A Chinese Tu-jia Nationality Pedigree With Mandibular Prognathism

Purpose:Mandibular prognathism is a common clinical problem with a substantial genetic component, but few susceptibility loci have been mapped. To investigate the etiology in a large autosomal-dominant inherited mandibular prognathism pedigree from China Tu-jia nationality.Methods:A large pedigree from China Tu-jia nationality was recruited. Family history material was collected using a detailed questionnaire. After detailed clinical evaluation, clinical photographs, panoramic and lateral cephalometric radiographs were performed on all the available family members. Family tree was drawn and the heritability model was determined. The peripheral blood of proband and other available individuals was obtained after achieving informed consent. Karyotyping analysis was performed in the part of family members. We analyzed the pedigree with6,090genome-wide single-nucleotide polymorphism (SNP) markers from Infinium HumanLinkage-12Beadchip (Illumina, San Diego, USA). Multipoint parametric linkage analyses were performed with MERLIN1.1.2for this pedigree. To find out the novel predisposing gene, candidate genes were resequencing using ABI3130sequence analyzer.Results:Autosomal dominant inheritance was determined according to the family tree. The family clinical feature was mandibular prognathism with normal maxillary, cancave profile, medial moral relationship, anterior crossbite and skeletal Class III malocclusion. There was no any chromosome abnormality found at the550-850band level. Linkage analysis identified a LOD score>3with the markers on chromosome2q14.3—2q22.1. ACVR2A, which encodes activin A type Ⅱ receptor, was resequenced as a candidate gene and no causal variation was identified.Conclusions:1、The clinical feature in this family was mandibular prognathism with normal maxillary, cancave profile, medial moral relationship, anterior crossbite and skeletal Class III malocclusion.2、The inheritance model in this family was autosomal dominant inheritance with incomplete penetrance.3、Chromosome abnormality was not the causal genetic variation in this family.4、A new genomic region,2q14.3—2q22.1, was identified linkage with the trait in the family. Another region,17q24.2-17q25.1, was also a candidate position. This linkage region provides target for susceptibility gene identification. Sanger resequencing did not find any causal variation in ACVR2A gene.