Kumar Arun, Shetty Jyoti, Kumar Bharath, Blanton Susan Halloran
Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, India.
Mol Vis. 2004 Jun 15;10:399-402.
To report the linkage analysis of retinitis pigmentosa (RP) in an Indian family.
Individuals were examined for symptoms of retinitis pigmentosa and their blood samples were withdrawn for genetic analysis. The disorder was tested for linkage to known 14 adRP and 22 arRP loci using microsatellite markers.
Seventeen individuals including seven affecteds participated in the study. All affected individuals had typical RP. The age of onset of the disease ranged from 8-18 years. The disorder in this family segregated either as an autosomal recessive trait with pseudodominance or an autosomal dominant trait. Linkage to an autosomal recessive locus RP28 on chromosome 2p14-p15 was positive with a maximum two-point lod score of 3.96 at theta=0 for D2S380. All affected individuals were homozygous for alleles at D2S2320, D2S2397, D2S380, and D2S136. Recombination events placed the minimum critical region (MCR) for the RP28 gene in a 1.06 cM region between D2S2225 and D2S296.
The present data confirmed linkage of arRP to the RP28 locus in a second Indian family. The RP28 locus was previously mapped to a 16 cM region between D2S1337 and D2S286 in a single Indian family. Haplotype analysis in this family has further narrowed the MCR for the RP28 locus to a 1.06 cM region between D2S2225 and D2S296. Of 15 genes reported in the MCR, 14 genes (KIAA0903, OTX1, MDH1, UGP2, VPS54, PELI1, HSPC159, FLJ20080, TRIP-Br2, SLC1A4, KIAA0582, RAB1A, ACTR2, and SPRED2) are either expressed in the eye or retina. Further study needs to be done to test which of these genes is mutated in patients with RP linked to the RP28 locus.
报告一个印度家庭中视网膜色素变性（RP）的连锁分析。
对个体进行视网膜色素变性症状检查，并采集血样进行基因分析。使用微卫星标记检测该疾病与已知的14个常染色体显性视网膜色素变性（adRP）和22个常染色体隐性视网膜色素变性（arRP）位点的连锁情况。
17人参与了研究，其中7人患病。所有患病个体均有典型的RP症状。发病年龄在8至18岁之间。该家庭中的疾病表现为具有假显性的常染色体隐性性状或常染色体显性性状。与2号染色体p14 - p15上的常染色体隐性位点RP28连锁呈阳性，在θ = 0时，D2S380的最大两点连锁值为3.96。所有患病个体在D2S2320、D2S2397、D2S380和D2S136位点的等位基因均为纯合。重组事件将RP28基因的最小关键区域（MCR）定位在D2S2225和D2S296之间1.06厘摩（cM）的区域内。
目前的数据证实了在第二个印度家庭中arRP与RP28位点的连锁关系。RP28位点先前在一个印度家庭中被定位在D2S1337和D2S286之间16厘摩的区域。该家庭中的单倍型分析进一步将RP28位点的MCR缩小至D2S2225和D2S296之间1.06厘摩的区域。在MCR中报告的15个基因里，有14个基因（KIAA0903、OTX1、MDH1、UGP2、VPS54、PELI1、HSPC159、FLJ20080、TRIP - Br2、SLC1A4、KIAA0582、RAB1A、ACTR2和SPRED2）在眼睛或视网膜中表达。需要进一步研究以检测这些基因中哪些在与RP28位点连锁的RP患者中发生了突变。
