Mutation survey of known LCA genes and loci in the Saudi Arabian population.
Mutation survey of known LCA genes and loci in the Saudi Arabian population.
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DOI：
10.1167/iovs.08-2589
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发表时间：
2009-03
影响因子：
4.4
通讯作者：
Chen R
中科院分区：
文献类型：
--
作者：
Li Y;Wang H;Peng J;Gibbs RA;Lewis RA;Lupski JR;Mardon G;Chen R
本研究的目的是对来自沙特阿拉伯的37个近亲LCA家族中所有已知的Leber先天性黑朦（LCA）基因和位点进行全面调查。采用直接PCR和测序技术筛选已知的13个LCA基因（GUCY2D、CRX、RPE65、TULP1、AIPL1、CRB1、RPGRIP1、LRAT、RDH12、IMPDH1、CEP290、RD3、LCA5）。此外，用这13个已知LCA基因和2个基因座周围的STR标记进一步筛选未发现突变的家族。在37个家族中的9个中发现了致病突变：5个在TULP1中，2个在CRB1中，1个在RPE65中，1个在GUCY2D中。已知基因突变仅占沙特家庭的24%，远低于欧洲人口（65%）。进行表型-基因型分析，以调查所有确定突变的家庭的LCA疾病外显率。所有鉴定的突变都被发现与疾病表型完全分离。另一方面，携带相同突变的不同患者，甚至在同一家庭中，疾病的严重程度也有所不同。此外，基于与STR和SNP标记的纯合性定位，一个家族可能映射到LCA3位点。这些结果强调了研究来自不同种族背景的LCA疾病家族以确定其他新的LCA疾病基因的重要性。此外，突变和疾病之间的完美分离表明LCA是完全渗透的。然而，携带相同突变的患者之间的表型差异表明，至少有一些临床表型差异是由于遗传背景、环境或其他因素的改变。
The purpose of this study was to perform a comprehensive survey of all known Leber congenital amaurosis (LCA) genes and loci in a collection of 37 consanguineous LCA families from Saudi Arabia. Direct PCR and sequencing were used to screen 13 known LCA genes (GUCY2D, CRX, RPE65, TULP1, AIPL1, CRB1, RPGRIP1, LRAT, RDH12, IMPDH1, CEP290, RD3, LCA5). In addition, families without mutations identified were further screened with STR markers around these 13 known LCA genes and two loci. Disease-causing mutations were identified in nine of the 37 families: five in TULP1, two in CRB1, one in RPE65, and one in GUCY2D. Mutations in known genes only accounted for 24% of the Saudi families—much less than what has been observed in the European population (65%). Phenotype-genotype analysis was carried out to investigate the LCA disease penetrance for all families whose mutations identified. All identified mutations were found to segregate perfectly with the disease phenotype. On the other hand, severity of the disease varies for different patients carrying the same mutation and even within the same family. Furthermore, based on homozygosity mapping with both STR and SNP markers, one family is likely to map to the LCA3 locus. These results underscore the importance of studying LCA disease families from different ethnic backgrounds to identify additional novel LCA disease genes. Furthermore, perfect segregation between mutation and disease indicates that LCA is fully penetrant. However, phenotypic variations among patients carrying the same mutation suggest that at least some of the variations in the clinical phenotype is due to modification from the genetic background, environment, or other factors.
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影响因子：
30.8
作者：
Gal, A;Li, Y;Vollrath, D
通讯作者：
Vollrath, D
影响因子：
30.8
作者：
Janecke, AR;Thompson, DA;Gal, A
通讯作者：
Gal, A
影响因子：
30.8
作者：
Sohocki, MM;Bowne, SJ;Daiger, SP
通讯作者：
Daiger, SP
影响因子：
9.8
作者：
Sohocki, MM;Sullivan, LS;Daiger, SP
通讯作者：
Daiger, SP
影响因子：
9.8
作者：
Friedman, James S.;Chang, Bo;Swaroop, Anand
通讯作者：
Swaroop, Anand