常染色体隐性遗传念珠状发一例及其家系基因突变研究

Autosomal recessive monilethrix： a case report and mutation analysis

目的 报道国内首例常染色体隐性遗传念珠状发,对患者及其父母桥粒芯糖蛋白4编码基因（DSG4）进行突变研究.方法 抽取1例念珠状发患儿及其父母外周血,提取血液基因组DNA,同时取100例健康汉族人基因组DNA样品作对照,采用PCR方法扩增DSG4基因16个外显子,并对产物进行测序分析.结果 患儿 DSG4基因存在2个杂合突变,突变1为第8外显子移位突变c.837delA（p.E280Rfs＊4）,突变2为第16外显子无义突变c.2389C＞ T（p.R797＊）.对其父母的基因分析证明,突变1来自其父亲,突变2来自其母亲.100例健康对照均未发现该杂合突变.结论 DSG4基因的2个杂合突变c.837delA（p.E280Rfs＊4）和c.2389C＞T（p.R797＊）导致该常染色体隐性遗传念珠状发家系的临床表型,2个突变均导致DSG4基因翻译的提前终止.

Objective To report the first case of autosomal recessive monilethrix in China,and to study the mutations in the desmoglein 4 （DSG4） gene in the patient and his parents.Methods Peripheral blood samples were obtained from an 11-year-old boy with monilethrix,his parents and 100 healthy human controls of Han nationality.Genomic DNA was extracted from these samples,and PCR was performed to amplify 16 exons of the DSG4 gene followed by DNA sequencing.Results There were 2 heterozygous mutations in the DSG4 gene in the patient,including a translocation mutation c.837delA （p.E280Rfs＊4） in exon 8 and a nonsense mutation c.2389C 〉 T （p.R797＊） in exon 16.Gene analysis in the parents revealed that the translocation mutation and nonsense mutation were inherited from the father and mother respectively.Neither of the two mutations was found in the 100 healthy controls.Conclusions The two heterozygous mutations c.837delA （p.E280Rfs＊4） and c.2389C 〉 T （p.R797＊） in the DSG4 gene,both of which lead to premature termination of translation of the DSG4 gene,may be responsible for the clinical phenotype of autosomal recessive monilethrix in this family.