Linkage of microsatellites to the AGXT gene on chromosome 2q37.3 and their role in prenatal diagnosis of primary hyperoxaluria type 1.

Defects in the AGXT gene mapped to chromosome 2q37.3 cause primary hyperoxaluria type 1 (PH1), one of the inherited disorders of endogenous oxalate overproduction. In order to identify diagnostically useful linkage markers in this region of chromosome 2 we have typed three microsatellite loci mapping to the q37 region of chromosome 2 in 192 individuals from 30 families. They were additionally studied for mutations and polymorphisms in the AGXT gene. Maximum lod scores of 29.1, 22.8 and 15.8 were obtained for D2S140, D2S125 and D2S395 respectively at recombination fractions (theta) of 0.001, 0.015 and 0.02. Confidence intervals for recombination as determined by the 'lod-1 rule' were 0.015, 0.05 and 0.06. Three recombinants were identified between AGXT and D2S125/D2S395, whereas no recombination between AGXT and D2S140 was observed. These data allow the calculation of the risk of incorrect prenatal diagnosis of PH1 based solely on linkage analysis with these extragenic markers.