先天性静止性夜盲家系和无色素性视网膜色素变性家系临床表型及突变基因的研究

Studies the clinical phenotypes and mutation disease-causing geness of congenital stationary night blindness pedigree and retinitis pigmentosa sine pigmento pedigree

目的研究先天性静止性夜盲家系和无色素性视网膜色素变性家系的致病基因突变及临床表型特征。方法收集在宁夏眼科医院就诊的1个先天性静止性夜盲(CSNB)和1个无色素性视网膜色素变性(RPSP)家系的临床资料,抽取患者家庭成员及其正常对照者外周静脉血,提取DNA;运用外显子结合目标区域捕获测序芯片进行检测,对检测结果进行分析后得到候选致病性突变位点。运用PCR和直接测序进行验证,确定致病性突变位点。结果 CSNB家系有3例患者,自幼夜盲,无进行性加重,ERG表现为暗视ERG,即a波正常、b波显著下降;EOG正常。RPSP家系有3例患者,自幼夜盲,逐渐加重。ERG检查与暗视ERG,a波、b波均重度下降;EOG显示光峰/暗谷明显降低。通过基因检测和生物信息分析,证实TRPM1基因p.R1025L为该家系的致病基因突变,MERTK基因p.R1443W为RPSP家系的致病基因突变。结论先天性静止性夜盲及无色素性视网膜色素变性根据眼底表现难以鉴别,ERG、EOG检查及结合基因突变检测分析,可为临床诊断提供可靠依据。

Objective To study the disease - causing genes and clinical phenotypes of the congenital stationary night blindness pedigree and retinitis pigmentosa sine pigmento pedigree. Methods One congenital stationary night blindness pedigree and one retinitis pigmentosa sine pigmento pedigree were recruited for this study. All the patients and family members received complete ophthalmic exam- inations. DNA was abstracted from patients, family members and controls. Using exon combined target region capture sequencing chip to screen the candidate disease -causing mutations. Polymerase chain reaction （PCR）and direct sequencing were used to confirm the dis- ease -causing mutations. Results 3 patients in the congenital stationary night blindness pedigree are nonprogressive blindness, ERG shows a normal a - wave but a striking reduction of the b - wave on the dark - adapted bright flash ERG, whose amplitude of the b - wave is smaller than that of the a - wave and responses to a single bright flash in the Schubert - Boruschein type of ERG pattern but a normal responses to EOG. 3 patients of the Retinitis pigmentosa sine pigmento pedigrees are progressive nyctalopia blindness from an early age. ERG shows a striking reduction of both a - wave and b - wave on the dark - adapted bright flash ERG. p. R1025L heterozygous missense mutation on TRPM1 gene in congenital stationary night blindness patients was detected, p. R1443W heterozygous missense mutation on MERTK gene in RPSP patients was detected by means of genetic tests and bio - information analysis. Conclusions Congenital stationary night blindness and Retinitis pigmentosa sine pigmento is difficult to identify according to fundus appearance, ERG, EOG examination combined with gene mutation detection and analysis can provide a reliable basis for clinical diagnose.