PITX1 and familial clubfoot with or without associated lower limb anomalies: Initially identified through a genome-wide linkage study in a five-generation clubfoot family with nine affected members, PITX1, a transcription factor from the bicoid-related homeodomain family, displayed significant linkage to the 5q31 locus with an LOD score of 3.31.42, 43, 44 A missense mutation (E310K) in PITX1 was identified within this family, segregating with clubfoot and absent in a control group of 500 individuals.