Genome scan, fine-mapping, and candidate gene analysis of non-syndromic cleft lip with or without cleft palate reveals phenotype-specific differences in linkage and association results.

Objectives: Non-syndromic orofacial clefts, i.e. cleft lip (CL) and cleft palate (CP), are among the most common birth defects.

AXIS inhibition protein 2, orofacial clefts and a family history of cancer.

Background: Cancer and congenital malformations occasionally may have a common etiology. The authors investigated whether families with one or more members affected by orofacial clefts (that is, families segregating orofacial clefts) had an increased cancer incidence when compared with control families.

Methods: The authors assessed 75 white families with nonsyndromic cleft lip with or without cleft palate (CL/P) and 93 white control families regarding a history of cancer.

The PDGF-C regulatory region SNP rs28999109 decreases promoter transcriptional activity and is associated with CL/P.

Human linkage and association studies suggest a gene(s) for nonsyndromic cleft lip with or without cleft palate (CL/P) on chromosome 4q31-q32 at or near the platelet-derived growth factor-C (PDGF-C) locus. The mouse Pdgfc(-/-) knockout shows that PDGF-C is essential for palatogenesis. To evaluate the role of PDGF-C in human clefting, we performed sequence analysis and SNP genotyping using 1048 multiplex CL/P families and 1000 case-control samples from multiple geographic origins.