Designation of the TARP syndrome and linkage to Xp11.23‐q13.3 without samples from affected patients

Abstract

The Robin sequence is a well-known cause of cleft palate and can be sporadic or familial, isolated or syndromic. We present a four-generation family with a lethal disorder inherited in an X-linked recessive pattern that includes Talipes equinovarus, Atrial septal defect, Robin sequence, and Persistence of the left superior vena cava. We have designated this disorder "TARP" syndrome. All affected males die in infancy of unknown causes. An X-chromosome linkage scan was performed using 14 unaffected members of a single large family and 40 STRP markers. The gene was mapped to an 11-cM region in Xp11.23-q13.3. Markers DXS1003 and DXS8092 flank the region and three-point linkage analyses revealed a maximum LOD score of 2.75 at marker DXS1039. We have designated this locus as TARP. This locus was mapped without genotyping any affecteds and demonstrates that rare, lethal disorders can be evaluated by genetic linkage, even when no affected probands are available for study.