Association of genetic variation of the transforming growth factor-alpha gene with cleft lip and palate

• Published in: American journal of human genetics 1989-09, Vol.45 (3), p.348-353
• Main Authors: ARDINGER, H. H, BUETOW, K. H, BELL, G. I, BARDACH, J, VANDEMARK, D. R, MURRAY, J. C
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Alleles; Biological and medical sciences; Child; Child, Preschool; Cleft Lip - genetics; cleft lip/palate; Cleft Palate - genetics; DNA Probes; Facial bones, jaws, teeth, parodontium: diseases, semeiology; genes; Genetic Markers; Genotype; Haplotypes; Humans; Infant; Medical sciences; Non tumoral diseases; Otorhinolaryngology. Stomatology; Polymorphism, Genetic; Polymorphism, Restriction Fragment Length; Transforming Growth Factors - genetics
• ISSN: 0002-9297; 1537-6605

Complex segregation analysis of pedigrees having nonsyndromic cleft lip with or without cleft palate (CL/P) (Chung et al. 1986; Marazita et al. 1986) has shown that a major-locus model best explains the observed recurrence of CL/P in Caucasian families. To identify this major gene, we compared the frequencies of 12 RFLPs at five loci-epidermal growth factor, transforming growth factor-alpha, epidermal growth factor receptor, glucocorticoid receptor, and estrogen receptor-in both a group of 80 subjects with nonsyndromic CL/P and 102 controls. These candidate genes were selected because studies in rodents had suggested their possible involvement in palatogenesis. A significant association was observed between two RFLPs at the transforming-growth-factor-alpha (TGFA) locus and the occurrence of clefting (P = .0047 and P = .0052). This suggests that either the TGFA gene itself or DNA sequences in an adjacent region contribute to the development of a portion of cases of CL/P in humans and provides an opportunity to begin to examine the molecular events underlying lip and palate formation.