Comprehensive survey of mutations in RP2 and RPGR in patients affected with distinct retinal dystrophies: Genotype-phenotype correlations and impact on genetic counseling
Comprehensive survey of mutations in RP2 and RPGR in patients affected with distinct retinal dystrophies: Genotype-phenotype correlations and impact on genetic counseling
复制标题
DOI：
10.1002/humu.20417
复制
发表时间：
2007-01-01
期刊：
影响因子：
3.9
通讯作者：
Rozet, Jean-Michel
中科院分区：
文献类型：
--
作者：
Pelletier, Valerie;Jambou, Marguerite;Rozet, Jean-Michel
X-连锁形式的视网膜色素变性（RP）（XLRP）占RP家族的10%至20%，并且主要由RP 2或RP GTR调节因子（RPGR）基因中的突变引起。我们报告了在127个法国家庭的队列中筛选这些基因，包括：1）93个RP家族病例，表明X连锁遗传，包括93个家族中的48个家族，在女性中表达，但没有男性到男性的传播; 2）7个RP的男性同胞; 3）25个散发的RP男性病例;和4）2个锥体营养不良（COD）。在93个RP家系中，共有5个排除了与RP 2和RP 3基因座的连锁，并从队列中删除。在88例家族性RP中发现14例RP 2突变，其中12例为新突变，在25例散发性RP中发现1例（4%）。在14个家族性病例中，有13个病例的女性未出现这种疾病的表达，而在14个家族中，有1个家族中的1名女性在第三个十年中出现RP。在80个家系中共发现42个RPGR突变，其中26个为新突变，包括：88个家族性病例中的69个（78.4%）; 7个男性同胞中的2个（28.6%）; 25个散发男性病例中的8个（32.0%）;以及2个COD中的1个。在69个家族性病例中，41个（59.4%）的女性患者未发现该病，而在69个家庭中，28个（40.6%）的患者至少有一名严重受累的女性。提示X4连锁传播的RP家族性病例中RP 2和RPGR突变的频率与其他地方报道的一致（RP 2：15.9% vs. 6-20%; RPGR：78.4% vs. 55-90%）。有趣的是，约30%的男性散发病例和30%的RP男性同胞携带RP 2或RPGR突变，证实了在前十年开始患有RP并导致30岁之前严重视力损害的男性患者中XLRP基因遗传筛查的相关性。(c)2006 Wiley-Liss，Inc.
X-linked forms of retinitis pigmentosa (RP) (XLRP) account for 10 to 20% of families with RP and are mainly accounted for by mutations in the RP2 or RP GTPase regulator (RPGR) genes. We report the screening of these genes in a cohort of 127 French family comprising: 1) 93 familial cases of RP suggesting X-linked inheritance, including 48 out of 93 families with expression in females but no male to male transmission; 2) seven male sibships of RP; 3) 25 sporadic male cases of RP; and 4) two cone dystrophies (COD). A total of 5 out of the 93 RP families excluded linkage to the RP2 and RP3 loci and were removed form the cohort. A total of 14 RP2 mutations, 12 of which are novel, were identified in 14 out of 88 familial cases of RP and I out of 25 sporadic male case (4%). In 13 out of 14 of the familial cases, no expression of the disease was noted in females, while in 1 out of 14 families one woman developed RP in the third decade. A total of 42 RPGR mutations, 26 of which were novel, were identified in 80 families, including: 69 out of 88 familial cases (78.4%); 2 out of 7 male sibship (28.6%); 8 out of 25 sporadic male cases (32.0%); and I out of 2 COD. No expression of the disease was noted in females in 41 out of 69 familial cases (59.4%), while at least one severely affected woman was recognized in 28 out of 69 families (40.6%). The frequency of RP2 and RPGR mutations in familial cases of RP suggestive of X4inked transmission are in accordance to that reported elsewhere (RP2: 15.9% vs. 6-20%; RPGR: 78.4% vs. 55-90%). Interestingly, about 30% of male sporadic cases and 30% of male sibships of RP carried RP2 or RPGR mutations, confirming the pertinence of the genetic screening of XLRP genes in male patients affected with RP commencing in the first decade and leading to profound visual impairment before the age of 30 years. (c) 2006 Wiley-Liss, Inc.