Further evidence for an association between genetic variation in transforming growth factor alpha and cleft lip and palate.

Ardinger et al. (1989) hypothesized that there might be a nonrandom association between clefting and RFLPs of candidate genes which have a role in palate formation. They reported a significant association between two RFLPs of transforming growth-factor alpha (TGFa) and clefting in a group of 80 patients with nonsyndromic cleft lip with or without cleft palate (CLIP) and in a group of 102 controls (P = .0047 for the TaqI RFLP, and P = .0052 for the BamHI RFLP). However, in another study of seven families with CLI P segregating in a dominant manner, none of the TGFa haplotype associations reported by Ardinger et al. was seen, and, in one family, clefting did not cosegregate with TGFa, ruling out tight linkage in these families (Hecht et al. 1990). We have genotyped the TaqI RFLP in 96 unrelated nonsyndromic patients with CLIP and in 100 unrelated controls. Of the patients, 62 (65%) were male, and 48 (51%) of the 94 for whom information was available had a family history of CLIP (n = 44) or cleft palate alone (n = 4). The high percentage of patients with a family history of clefting probably reflects our method of ascertainment (mainly through newspaper articles in which we encouraged participation from familial cases). There were 20 patients (21 % ) with bilateral CL + P, 51 (54%) with unilateral CL + P, four (4%) with bilateral CL, and 19 (20%)