A 2ND LOCUS (GLC3B) FOR PRIMARY CONGENITAL GLAUCOMA (BUPHTHALMOS) MAPS TO THE 1P36 REGION

Primary congenital glaucoma (gene symbol: GLC3) is an ocular disorder that occurs for 0.01-0.04% of blind people. In the majority of familia l cases reported so far, this condition is inherited as an autosomal r ecessive trait. We have recently used a group of 17 GLC3 families with a minimum of two affected offspring and consanguinity in most of the parental generation and mapped the first GLC3 locus (GLC3A) to the 2p2 1 region. Six families did not show any linkage to the GLC3A locus and thus provided evidence for genetic heterogeneity of this disorder. A total of eight families unlinked to the 2p21 region were used to searc h for the chromosomal location of the second GLC3 locus. Herein, we de scribe mapping of a new locus (designated GLC3B) for primary congenita l glaucoma to the short arm of chromosome 1 (1p36.2-36.1) that is situ ated centromeric to the neuroblastoma and Charcot-Marie-Tooth type 2A (CMT2A) loci. A total of 17 DNA markers were genotyped from this regio n of chromosome 1. Four families showed no recombination with the two markers D1S2834 and D1S402 with a maximum lod score of 4.510 and 4.157 respectively. Pairwise and multipoint linkage analysis and inspection of the haplotypes revealed that the remaining four families are not l inked to this part of chromosome 1, thus providing further evidence th at at least one more locus for the autosomal recessive form of GLC3 mu st exist in the genome. Based on the recombination events, the overall linkage map of this region is: tel-D1S1192-D1S1635-D1S1193 -(D1S1597/ D1S489/D1S228) - [GLC3B/D1S2834/D1S402] - (D1S1176/D1S507/D1S407) - D1 S2728-(MFAP2/D1S170) - D1S1368-D1S436-D1S1592-cen.