1个X连锁隐性遗传视网膜色素变性家系的基因突变检测

Gene mutation detection in an X-linked recessive retinitis pigmentosa family

目的研究1个侗族X连锁隐性遗传视网膜色素变性(RP)家系的临床表型和致病变异。方法选取湖南怀化的1个侗族RP家系进行调查研究,对该家系进行专业的眼部检查,提取DNA,利用全外显子组测序技术对该家系的先证者(Ⅲ1)和患者(Ⅱ1)进行分析,寻找致病基因。对患者及其亲属进行Sanger测序验证。结果此家系遗传方式为X连锁隐性遗传。先证者,男,13岁,自幼视力差,右眼裸眼视力0.4,左眼裸眼视力0.5,散瞳见晶状体透明,视乳头界清,色淡,视网膜广泛色素沉积。患者Ⅱ1与先证者临床表型相似。基因检测结果表明,患者RPGR基因存在g.ORF15:653-654delAG(p.Glu802fs)纯合缺失突变,查阅资料发现,中国侗族人群中尚未报道过该突变。此突变致男性患者产生严重的临床表型,女性携带者一般表现出不同程度的变性近视。结论该家系致病变异为g.ORF15:653-654delAG(p.Glu802fs)的缺失突变,首次在中国侗族家系中报道,为该家系的遗传咨询和产前诊断奠定了基础,也有利于深入研究XLRP的分子病理诊断和基因治疗。

Objective To study the clinical phenotypes and pathogenic variants in a Dong ethnic family with X-linked recessive retinitis pigmentosa(RP).Methods A Dong RP family in Huaihua,Hunan province,was selected for investigation and research.Professional eye examinations were performed on the family.DNA was extracted,and analyze proband(Ⅲ1)and patient(Ⅱ1)of the family using whole exome sequencing to identify pathogenic genes.The patient and their relatives were validated by Sanger sequencing.Results The genetic manner of this family was X-linked recessive inheritance.The proband,male,13-year-old,had poor vision since childhood,with a right eye naked visual acuity of 0.4 and a left eye naked visual acuity of 0.5.His dilated pupils showed a clear lens,clear and pale optic papillary borders,and extensive retinal pigmentation.The clinical phenotype of patientⅡ1 was similar to that of the proband.Genetic testing showed that the patient had a pure deletion mutation g.ORF15:653-654delAG(p.Glu802fs)in the RPGR gene,and a review of the data revealed that this mutation has not been reported in the Chinese Dong population.This mutation leads to severe clinical phenotypes in male patients,while female carriers generally exhibit varying degrees of degenerative myopia.Conclusion The pathogenic mutation in this family is the deletion mutation of g.ORF15:653-654delAG(p.Glu802fs),which has been reported for the first time in the Dong family of China,lays the foundation for genetic counseling and prenatal diagnosis in this family,and facilitates in-depth research of molecular pathology and gene therapy for XLRP.