Mutation analysis of 272 Spanish families affected by autosomal recessive retinitis pigmentosa using a genotyping microarray

[摘要] Purpose: Retinitis pigmentosa (RP) is agenetically heterogeneous disorder characterized by progressive loss ofvision. The aim of this study was to identify the causative mutationsin 272 Spanish families using a genotyping microarray. Methods: 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 werealso classified by clinical criteria: 86 juveniles and 186 typical RPfamilies. Haplotype and sequence analysis were performed to identifythe second mutated allele. Results: At least one-gene variant wasfound in 14% and 16% of the juvenile and typical RP groupsrespectively. Further study identified four new mutations, providingboth causative changes in 11% of the families. Retinol Dehydrogenase 12(RDH12) was the most frequently mutated gene in the juvenile RPgroup, and Usher Syndrome 2A (USH2A) and Ceramide Kinase-Like (CERKL)werethemostfrequentlymutatedgenesinthetypicalRPgroup.Theonlyvariant found in CERKL was p.Arg257Stop, the most frequentmutation. Conclusions: The genotyping microarraycombined with segregation and sequence analysis allowed us to identifythe causative mutations in 11% of the families. Due to the low numberof characterized families, this approach should be used in tandem withother techniques.

[学科分类] 生物化学/生物物理