Linkage analysis narrows the critical region for oculodentodigital dysplasia to chromosome 6q22-q23

Oculodentodigital dysplasia (ODDD) is an autosomal dominant condition with high penetrance and variable expressivity. The anomalies of the craniofacia l region, eyes, teeth, and limbs indicate abnormal morphogenesis during ear ly fetal development. Neurologic abnormalities occur later in life and appe ar to be secondary to white matter degeneration and basal ganglia changes. In familial cases, the dysmorphic and/or neurodegenerative components of th e phenotype can be more severe and/or present at a younger age in subsequen t generations, suggesting genetic anticipation. These clinical features sug gest that the ODDD gene is pleiotropic with important functions throughout pre- and postnatal development. We have performed two-point linkage analysi s with seven ODDD families and 19 microsatellite markers on chromosome 6q s panning a genetic distance of approximately 11 cM in males and 20 cM in fem ales. We have refined the location of the ODDD gene between DNA markers D6S 266/D6S261 (centromeric) and D6S1639 (telomeric), an interval of 1.01 (male ) to 2.87 (female) cM. The strongest linkage was to DNA marker D6S433 (Z(ma x) = 8.96, theta(max) = 0.001). Families show significant linkage to chromo some 6q22-q23 and no evidence for genetic heterogeneity. (C) 1999 Academic Press.