Genotyping microarray: mutation screening in Spanish families with autosomal dominant retinitis pigmentosa.
OBJECTIVE
Presently, 22 genes have been described in association with autosomal dominant retinitis pigmentosa (adRP); however, they explain only 50% of all cases, making genetic diagnosis of this disease difficult and costly. The aim of this study was to evaluate a specific genotyping microarray for its application to the molecular diagnosis of adRP in Spanish patients.


METHODS
We analyzed 139 unrelated Spanish families with adRP. Samples were studied by using a genotyping microarray (adRP). All mutations found were further confirmed with automatic sequencing. Rhodopsin (RHO) sequencing was performed in all negative samples for the genotyping microarray.


RESULTS
The adRP genotyping microarray detected the mutation associated with the disease in 20 of the 139 families with adRP. As in other populations, RHO was found to be the most frequently mutated gene in these families (7.9% of the microarray genotyped families). The rate of false positives (microarray results not confirmed with sequencing) and false negatives (mutations in RHO detected with sequencing but not with the genotyping microarray) were established, and high levels of analytical sensitivity (95%) and specificity (100%) were found. Diagnostic accuracy was 15.1%.


CONCLUSIONS
The adRP genotyping microarray is a quick, cost-efficient first step in the molecular diagnosis of Spanish patients with adRP.
Servicio de Genética, IIS Fundación Jiménez Díaz, Madrid, Spain. fblancok@fjd.es
Fiona
F
Blanco-Kelly
María
M
García-Hoyos
Marta
M
Cortón
Almudena
A
Avila-Fernández
Rosa
R
Riveiro-Álvarez
Ascensión
A
Giménez
Inma
I
Hernan
Miguel
M
Carballo
Carmen
C
Ayuso
D016477:Artifacts; D005136:Eye Proteins / Q000235:genetics*; D005799:Genes, Dominant; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D010375:Pedigree; D012174:Retinitis Pigmentosa / Q000175:diagnosis* / Q000235:genetics; D012243:Rhodopsin / Q000235:genetics*; D012680:Sensitivity and Specificity; D013030:Spain; D044465:White People / Q000235:genetics*
D005136:Eye Proteins; D012243:Rhodopsin