Nonsyndromic congenital retinal nonattachment gene maps to human chromosome band 10q21

Nonsyndromic congenital retinal nonattachment (NCRNA) comprises congenital insensitivity to light, massive retrolental mass, shallow anterior chamber, microphthalmia, and nystagmus. We searched for the location of the gene responsible for an autosomal recessive form of NCRNA by using DNA samples from 36 individuals from a founding population. To this end we applied homozygosity mapping and a DNA pooling strategy using genomewide screen polymorphic microsatellite markers. We used two DNA pools, one pool contained DNA from 16 individuals affected with NCRNA. The second pool contained DNA from 20 normal carrier individuals, the parents of the patients. The polymorphic microsatellite markers were polymerase chain reaction (PCR)-amplified in each DNA pool; the PCR products were electrophoresed on polyacrylamide gels and visualized by silver staining. The banding patterns from DNA pools of affected and unaffected persons were compared, and linkage was detected between the NCRNA and D10S1225, a marker in 10q21. To confirm linkage of NCRNA to chromosome 10q21 by homozygosity mapping, the patients and their carrier parents were genotyped for a number of other microsatellite polymorphic markers in the 10q21region. Statistically significant linkage was observed with multiple polymorphic markers in the 10q21 region. At straight theta = 0 with markers D10S1225, D10S1428, D10S1422, and D10S1418 maximum LOD scores of 3.74, 3.58, 3. 79, and 3.48 were generated, respectively. TDT P values for markers D10S1225 and D10S1418 were 0.0000021 and 0.000021, respectively.