一个遗传性釉质发育不全家系的临床及致病基因研究

Clinical and Genetic Analysis of A Pedigree Affected with Amelogenesis Imperfecta

目的:探讨一个遗传性釉质发育不全(amelogenesis imperfecta,AI)家系的临床表型和致病基因,为该病的临床诊断和遗传咨询提供依据。方法:收集先证者及其家系成员的临床资料,同时采集家系成员的外周血,提取全基因组DNA,全外显子组测序检测可能的致病基因,进一步对候选变异进行Sanger测序验证。结果:该家系患病成员的临床表现为全口牙呈黄褐色,釉质质地较软,剥脱磨损,牙面粗糙不规则,釉质密度接近牙本质,符合AI中的亚型钙化不全型的临床表型;同时该家系患病成员在FAM83H基因第5外显子上均存在c.1366C>T(p.Gln456*)的无义突变,已有该变异致病性的相关报道,且未患病的家系成员未发现上述突变。结论:该家系患有常染色体显性遗传钙化不全型AI,FAM83H基因第5外显子c.1366C>T(p.Gln456*)的无义突变是该家系的致病原因,本研究为该家系的诊断和遗传咨询提供依据。

Objective:To explore the clinical and genetic characteristics of a Chinese pedigree affected with amelogenesis imperfecta(AI).Methods:Clinical data of the pedigree members were collected and genomic DNA were extracted from peripheral blood samples.Whole exome sequencing was used to identify mutations and confirmed by Sanger sequencing.Results:Clinical characteristics of all the affected family members found in the present study were including:all teeth with yellowish coloration,enamel with an irregular rough surface,remaining enamel was softer than normal,and the enamel density could not be distinguished from dentin,which were consistent with autosomal dominant hypocalcified AI(ADHCAI).The proband was found to carry a known nonsense mutation(c.1366C>T)in exon 5 of the FAM83H gene,causing a truncated protein(p.Gln456).In addation,the mutation was cosegregated among affected family members with ADHCAI phenotype but not in those that were unaffected.Conclusion:The nonsense mutation(c.1366C>T)was identified in FAM83H gene in the pedigree associated with ADHCAI,which provided a basis for molecular diagnosis and genetic counseling for this pedigree.