III型神经中丝蛋白基因与中国高度近视人群相关性的研究

为了检测peripherin基因（PRPH）的突变与高度近视的病因有无相关关系，采用PCR-SSCP检测180例中国人高度近视先证者及60例正常人中PRPH基因所有外显子有无突变；对有突变的外显子区域进行克隆测序。结果表明，分析180例高度近视先证者PRPH基因编码区9个外显子及其邻近内含子，分别发现有下列核苷酸改变：密码子21TTC→TTT(Phe21Phe、4/180),nt2138C→G（IVS3、1/180），密码子277GCC→ACC（Ala277Thr、8/180），密码子237CCA→TCA（Arg237stop、1/180），密码子292GCG→GCA(Ala292Ala,1/180),密码子361CUG→CUC（Leu361Leu,12/180），密码子369AAA→AAG（Lys369Lys,12/180），nt3331G→C（IVS7、3/180），其中GCC277ACC为错义突变（Ala277Thr）；CCA237TCA为无义突变（Arg237stop）；密码子361CUG→CUC，密码子369AAA→AAG属于同义突变并且相连锁。Ala277Thr突变尚存在于正常人群中（1/60），亦存在于患者正常亲属中；Arg237stop仅见于一个常染色体隐性遗传家系的患者中，为杂合性突变。分析180例高度近视先证者PRPH基因，未发现致病突变，可排除PRPH基因与高度近视病因的相关性。在中国人群中PRPH基因有多种变异。 Variation of the Peripherin Gene in Chinese with or Without High Myopia LI Jiang1,ZHANG Qing-jiong1,FU Rong2,XIAO Xue-shan1,LI Jia-zhang3,ZHANG Feng-sheng4, LI Shi-qiang1,LI Wei5,LI Tuo3,JIA Xiao-yun1,GUO Li1,GUO Xiang-ming 1.Zhongshan Ophthalmic Center,Sun Yat-sen University,Guangzhou 510060,China; 2.Shenzhen Municipal People's Hospital,Shenzhen 518000,China; 3.Department of Opthalmolgy,The people's Hospital of Enshi Autonomous Prefecture,Enshi 445000,Hubei,China; 4.Chaoju Eye Hospital,Baotou,Inner Mongolia 014000,China; 5.Shenzhen 2nd People's Hopital,Shenzhen 518000,China Abstract:To analyze the relationship of the peripherin gene(PRPH,OMIM17071) mutations with high myopia,genomic DNA was collected from 180 probands with high myopia (≤-6.0 dipoters) and 60 unrelated persons without high myopia.The coding sequences of PRPH gene in 240 subjects were analyzed using exon-by-exon PCR-heteroduplex-SSCP analysis and sequencing.Variations at codon21TTC→TTT(Phe21Phe、4/180),nt2138C→G（IVS3、1/180），codon277 GCC→ACC（Ala277Thr、8/180），codon237 CCA→TCA （Arg237stop、1/180），codon292CCG→CCA (Ala292Ala,1/180),codon361CUG→CUC（Leu361Leu,12/180），codon369 AAA→AAG（Lys369Lys,12/180）,nt3331G→C（IVS7、3/180）were detected in a number of probands as indicated in the blanket.Of the 8 variations one( codon 277,G→A,Ala277Thr) is a missense mutation identified in 8 of the 180patients and one of 60 controls;The mutation of codon361 and codon 369were synonymous one and linkage each other;Another one(codon237,CCA→TCA,Arg237stop) is a heterozygous nonsense mutation identified in one patient with autosomal recessive inheritance mode population but not in the 60 normal controls.The others were synonymous mutations.Eight nucleotide variations were found in the PRPH gene.We found no evidence that mutations in the PRPH gene are responsible for the high myopia in Chinese. Key words：high myopia; peripherin gene; PCR-SSCP

Variation of the Peripherin Gene in Chinese with or Without High Myopia

To analyze the relationship of the peripherin gene(P.RPH,OMIM17071) mutations with high myopia,ge-nomic DNA was collected from 180 probands with high myopia (^ - 6. 0 dipoters) and 60 unrelated persons without high myopia. The coding sequences of PRPH gene in 240 subjects were analyzed using exon-by-exon PCR-het-eroduplex-SSCP analysis and sequencing. Variations at codon21TTC-TTT(Phe21Phe,4/180) ,nt2138C-G(IVS3,l/ 180),codon277 GCC- ACC( Ak277Tru\ 8/180) , codon237 CCA--TCA (Arg237stop, 1/180) , codon292CCG- CCA ( Ala292Ala, 1/180) ,codon361CUG--CUC(Leu361Leu, 12/180) ,codon369AAA-AAG(Lys369Lys, 12/180) ,nt3331G-C(IVS7>3/180)were detected in a number of probands as indicated in the blanket. Of the 8 variations one( codon 277,G-A, Ala277Thr) is a missense mutation identified in 8 of the 180patients and one of 60 controls j The mutation of codon361 and codon 369were synonymous one and linkage each other; Another one(codon237,CCA->-TCA, Arg237stop) is a heterozygous nonsense mutation identified in one patient with autosomal recessive inheritance mode population but not in the 60 normal controls. The others were synonymous mutations. Eight nucleotide variations were found in the PRPH gene. We found no evidence that mutations in the PRPH gene are responsible for the high myopia in Chinese.