Ávila-Fernández Almudena, Cantalapiedra Diego, Aller Elena, Vallespín Elena, Aguirre-Lambán Jana, Blanco-Kelly Fiona, Corton M, Riveiro-Álvarez Rosa, Allikmets Rando, Trujillo-Tiebas María José, Millán José M, Cremers Frans P M, Ayuso Carmen
Genetics Department, IIS-Fundación Jiménez Díaz, Madrid, Spain.
Mol Vis. 2010 Dec 3;16:2550-8.
Retinitis pigmentosa (RP) is a genetically heterogeneous disorder characterized by progressive loss of vision. The aim of this study was to identify the causative mutations in 272 Spanish families using a genotyping microarray.
272 unrelated Spanish families, 107 with autosomal recessive RP (arRP) and 165 with sporadic RP (sRP), were studied using the APEX genotyping microarray. The families were also classified by clinical criteria: 86 juveniles and 186 typical RP families. Haplotype and sequence analysis were performed to identify the second mutated allele.
At least one-gene variant was found in 14% and 16% of the juvenile and typical RP groups respectively. Further study identified four new mutations, providing both causative changes in 11% of the families. Retinol Dehydrogenase 12 (RDH12) was the most frequently mutated gene in the juvenile RP group, and Usher Syndrome 2A (USH2A) and Ceramide Kinase-Like (CERKL) were the most frequently mutated genes in the typical RP group. The only variant found in CERKL was p.Arg257Stop, the most frequent mutation.
The genotyping microarray combined with segregation and sequence analysis allowed us to identify the causative mutations in 11% of the families. Due to the low number of characterized families, this approach should be used in tandem with other techniques.
视网膜色素变性（RP）是一种具有遗传异质性的疾病，其特征为进行性视力丧失。本研究的目的是使用基因分型微阵列鉴定272个西班牙家庭中的致病突变。
使用APEX基因分型微阵列对272个不相关的西班牙家庭进行研究，其中107个患有常染色体隐性视网膜色素变性（arRP），165个患有散发性视网膜色素变性（sRP）。这些家庭还根据临床标准进行了分类：86个青少年家庭和186个典型视网膜色素变性家庭。进行单倍型和序列分析以鉴定第二个突变等位基因。
在青少年和典型视网膜色素变性组中，分别有14%和16%的家庭发现了至少一种基因变异。进一步研究鉴定出四个新突变，在11%的家庭中提供了致病变化。视黄醇脱氢酶12（RDH12）是青少年视网膜色素变性组中最常发生突变的基因，而Usher综合征2A（USH2A）和神经酰胺激酶样蛋白（CERKL）是典型视网膜色素变性组中最常发生突变的基因。在CERKL中发现的唯一变异是p.Arg257Stop，这是最常见的突变。
基因分型微阵列与分离和序列分析相结合，使我们能够在11%的家庭中鉴定出致病突变。由于已鉴定的家庭数量较少，这种方法应与其他技术联合使用。
