Two pedigrees segregating Duane's retraction syndrome as a dominant trait map to the DURS2 genetic locus

PURPOSE. The genetic bases of Duane's retraction syndrome (DRS) were investigated to determine its molecular etiologies. In prior studies, the transcription factors SALL4 and HOXA1 were identified as the genes mutated in DRS with radial anomalies, and in DRS with deafness, vascular anomalies, and cognitive deficits, respectively. Less is known, 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, two pedigrees have been ascertained that segregate DRS as a dominant trait. METHODS. Members of two large dominant DRS pedigrees were enrolled in an ongoing study of the genetic basis of the congenital cranial dysinnervation disorders, and linkage analysis was conducted to determine whether their DRS phenotype maps to the DURS2 locus. RESULTS. By haplotype analysis, the DRS phenotype in each family cosegregates with markers spanning the DURS2 region. Linkage analysis reveals maximum lod scores > 2, establishing that the DRS phenotype in these two pedigrees maps to the DURS2 locus. CONCLUSIONS. 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 understanding of the DURS2 phenotype, as described in the companion paper.