Char Syndrome, an Inherited Disorder With Patent Ductus Arteriosus, Maps to Chromosome 6p12-p21

Abstract

Background —Patent ductus arteriosus (PDA) is a relatively common form of congenital heart disease. Although polygenic inheritance has been implicated, no specific gene defects causing PDA have been identified to date. Thus, a positional cloning strategy was undertaken to determine the gene responsible for the Char syndrome, an autosomal dominant disorder characterized by PDA, facial dysmorphism, and hand anomalies. Methods and Results —A genome scan was performed with 46 members of 2 unrelated families in which the disease was fully penetrant but the phenotype differed. Significant linkage was achieved with several polymorphic DNA markers mapping to chromosome 6p12-p21 (maximal 2-point LOD score of 8.39 with D6S1638 at θ=0.00). Haplotype analysis identified recombinant events that defined the Char syndrome locus with high probability to a 3.1-cM region between D6S459/D6S1632/D6S1541 and D6S1024. Conclusions —A familial syndrome in which PDA is a common feature was mapped to a narrow region of chromosome 6p12-p21. Additional analysis with other families and polymorphic markers as well as evaluation of potential candidate genes should lead to the identification of the Char syndrome gene, which will provide insights into cardiogenesis as well as limb and craniofacial development.