Riazuddin S Amer, Zulfiqar Fareeha, Zhang Qingjiong, Yao Wenliang, Li Shouling, Jiao Xiaodong, Shahzadi Amber, Amer Muhammad, Iqbal Muhammad, Hussnain Tayyab, Sieving Paul A, Riazuddin Sheikh, Hejtmancik J Fielding
Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, MD 20892-1860, USA.
Mol Vis. 2006 Oct 26;12:1283-91.
To localize and identify the gene and mutations causing autosomal recessive retinitis pigmentosa (RP) in consanguineous Pakistani families.
Families were ascertained and patients underwent complete ophthalmological examinations. Blood samples were collected and DNA was extracted. A genome-wide scan was performed using 382 polymorphic microsatellite markers on genomic DNA from affected and unaffected family members, and lod scores were calculated.
A genome-wide scan of 50 families gave a lod score of 7.4172 with D5S2015 using HOMOG1. RP in all 4 linked families mapped to a 13.85 cM (14.87 Mb) region on chromosome 5q31-33 flanked by D5S2090 and D5S422. This region harbors the PDE6A gene, which is known to cause autosomal recessive RP. Sequencing of PDE6A showed a homozygous single base pair change; c.889C->T, single base pair insertion; c.2218-2219insT, and single base pair substitution in the splice acceptor site; IVS10-2A->G in each of three families. In the fourth family linked to this region, no disease-causing mutation was identified in the PDE6A gene.
These results provide strong evidence that mutations in PDE6A result in recessive RP in three consanguineous Pakistani families. Although a fourth family was linked to markers in the 5q31-33 interval, no mutation was identified in PDE6A.
定位并鉴定导致巴基斯坦近亲家庭中常染色体隐性遗传性视网膜色素变性（RP）的基因及突变。
确定相关家庭，患者接受全面眼科检查。采集血样并提取DNA。使用382个多态性微卫星标记对患病和未患病家庭成员的基因组DNA进行全基因组扫描，并计算连锁对数。
对50个家庭进行全基因组扫描，使用HOMOG1软件分析D5S2015时连锁对数为7.4172。所有4个连锁家庭中的RP均定位于5号染色体5q31 - 33上一个13.85厘摩（14.87兆碱基）的区域，两侧分别为D5S2090和D5S422。该区域包含已知可导致常染色体隐性RP的PDE6A基因。对PDE6A基因进行测序发现，三个家庭中均存在纯合单碱基对改变：c.889C→T、单碱基对插入：c.2218 - 2219insT以及剪接受体位点的单碱基对替换：IVS10 - 2A→G。在与该区域连锁的第四个家庭中，未在PDE6A基因中鉴定出致病突变。
这些结果提供了有力证据，表明PDE6A基因突变导致三个巴基斯坦近亲家庭出现隐性RP。尽管第四个家庭与5q31 - 33区间的标记连锁，但未在PDE6A基因中鉴定出突变。
