To determine the molecular etiologies of Duane’s retraction syndrome (DRS), we are investigating its genetic bases. We have previously identified the transcription factors SALL4 and HOXA1 as the genes mutated in DRS with radial anomalies, and in DRS with deafness, vascular anomalies, and cognitive deficits, respectively. We know less, however, about the genetic etiology of DRS when it occurs in isolation, and only one genetic locus for isolated DRS, the DURS2 locus on chromosome 2, has been mapped to date. Toward the goal of identifying the DURS2 gene, we have ascertained and studied two pedigrees that segregate DRS as a dominant trait.
We enrolled members of two large dominant DRS pedigrees into our ongoing study of the genetic basis of the congenital cranial dysinnervation disorders, and conducted linkage analysis to determine if their DRS phenotype maps to the DURS2 locus.
By haplotype analysis, the DRS phenotype in each family co-segregates with markers spanning the DURS2 region, and linkage analysis reveals maximum lod scores of >2, establishing that the DRS phenotype in these two pedigrees maps to the DURS2 locus.
These two pedigrees double the published pedigrees known to map to the DURS2 locus, and can thus contribute toward the search for the DURS2 gene. The affected members represent a genetically defined population of DURS2-linked DRS individuals, and hence studies of their clinical and structural features can enhance our understanding of the DURS2 phenotype, as described in the companion paper.