一角膜营养不良家系的TGFBI基因突变

Pathogenic mutation of TGFBI gene in a family with corneal dystrophy

目的对一角膜营养不良家系的致病基因进行检测,明确该家系角膜营养不良的致病基因突变位点。方法采集先证者及其家系成员外周血标本,提取基因组DNA,采用全外显子组测序筛查先证者致病基因及突变位点,并通过Sanger测序对先证者及其家系成员DNA样本进行验证。结果全外显子测序结果显示,先证者5号染色体上的转化生长因子β诱导基因(TGFBI)4号外显子发生c.370 C>T(p.R124C)杂合突变,8号外显子发生c.1007 A>T(p.E336V)杂合突变。Sanger测序验证发现患者父亲及家系其他患者TGFBI基因也发生c.370 C>T(p.R124C)杂合突变,患者母亲及家系其他正常成员未见TGFBI基因发生突变。TGFBI基因c.370 C>T(p.R124C)突变与疾病表型共分离。结论TGFBI基因c.370 C>T(p.R124C)杂合突变是导致该家系角膜营养不良的致病原因。

Objective To detect the pathogenic genes of a family with corneal dystrophy,and identify the mutation sites of the pathogenic genes.Methods The peripheral blood samples from the proband and his family members were collected,and genomic DNA was extracted.The pathogenic genes and mutation sites of the proband were screened by whole exome sequencing(WES),and the DNA of the proband and his family members were verified by Sanger sequencing.Results The results of WES showed that the proband had a c.370 C>T(p.R124C)heterozygous mutation in exon 4 and a c.1007 A>T(p.E336V)heterozygous mutation in exon 8 of the TGFBI gene on chromosome 5.Sanger sequencing found that the patient′s father and other patients in the family also had a c.370 C>T(p.R124C)mutation in the TGFBI gene.No any mutation of the TGFBI gene was detected in the patient′s mother and normal members of the family.It was indicated that the c.370 C>T(p.R124C)heterozygous mutation of the TGFBI gene was co-segregated with the disease phenotype.Conclusion The heterozygous mutation of c.370 C>T(p.R124C)in the TGFBI gene may be the pathogenic mutation of corneal dystrophy in the family.