A novel locus on 19q13 associated with autosomal-dominant macular dystrophy in a large Greek family.
A novel locus on 19q13 associated with autosomal-dominant macular dystrophy in a large Greek family.
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19q13 上的一个新位点与希腊一个大家族的常染色体显性黄斑营养不良相关。
DOI：
10.1136/jmg.2005.040188
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发表时间：
2006
影响因子：
4
通讯作者：
Zhang,K
中科院分区：
文献类型：
--
作者：
Yang,Z;Kitsos,G;Tong,Z;Payne,M;Gorezis,S;Psilas,K;Grigoriadou,M;Zhao,Y;Kamaya,S;Aperis,G;Petersen,MB;Zhang,K
目的：探讨常染色体显性黄斑营养不良（MCDR5）在希腊一个大家族中的临床特征和相关基因位点。方法：对单个家庭26名成员进行临床检查和静脉穿刺。使用400个微卫星标记进行全基因组连锁扫描，这些标记分布在整个人类基因组中，平均间隔为10 cM。结果：该研究家族的14名成员表现出该疾病的临床特征，包括中央视力下降和视网膜后极黄斑异常。对已知与黄斑营养不良相关的基因座的分析没有显示出正相关。全基因组连锁扫描显示与19q染色体连锁，在θ = 0处，疾病与标记位点D19S412之间的最大LOD评分为5.809，为2点。根据重组事件，疾病间隔定位在染色体19q上的标记D19S420和D19S540之间，跨度约3.8 cM，在已知包含120个已知基因/转录本的区域。对其中11个基因/转录本进行了测序，未发现致病突变。结论：本研究描述了19q上一个与常染色体显性黄斑营养不良相关的新位点，命名为MCDR5。需要对其他家庭成员进行进一步研究，以进一步缩小间隔并确定致病基因。MCDR5的研究将有助于阐明这种黄斑疾病和其他黄斑疾病的潜在致病机制，包括年龄相关性黄斑变性。
Objective:To describe the clinical features of and genetic locus associated with autosomal-dominant macular dystrophy (MCDR5) in a large Greek family.Methods:26 members of a single family underwent clinical examinations and venepuncture. A genomewide linkage scan using 400 microsatellite markers distributed with an average spacing of 10 cM throughout the human genome.Results:14 members of the study family exhibited clinical features of the disease including decreased central vision and macular abnormalities in the posterior pole of the retina. Analysis of loci known to be associated with macular dystrophy did not show positive linkage. A genomewide linkage scan showed linkage to chromosome 19q, with a two-point maximum LOD score of 5.809 at θ = 0 between the disease and marker locus D19S412. On the basis of recombination events, the disease interval was localised between markers D19S420 and D19S540 on chromosome 19q, at a span of about 3.8 cM, in an area known to contain 120 known genes/transcripts. Eleven of these genes/transcripts were sequenced, and no disease-causing mutation was identified.Conclusions:This study describes a new locus on 19q associated with autosomal-dominant macular dystrophy, designated as MCDR5. Additional study of other family members will be necessary to further narrow the interval and identify the responsible gene. The study of MCDR5 will aid in elucidation of the underlying pathogenic mechanisms for this and other macular diseases, including age-related macular degeneration.