American journal of medical genetics. Part A

Association of chromosomal regions 3p21.2, 10p13, and 16p13.3 with nonsyndromic cleft lip and palate.

PMID 14755462


Approximately 4,000 babies with nonsyndromic cleft lip with or without cleft palate (NSCLP) are born each year in the United States. Because NSCLP exhibits both etiologic and genetic heterogeneity, attempts to identify the underlying genetic causes have met with limited success and the pursuit of early promising findings have yielded mixed results. Two recent genomic scans identified a number of suggestive regions; some of these results have been supported by our lab and others in subsequent studies. Using our NSCLP multiplex family population, we were able to provide additional supportive evidence for association to the regions 2q37, 11p12-14, 12q13, and 16p13.11-p12 that were identified in the genomic scans. However, there remains a number of additional viable candidate genes and regions that have not been sufficiently investigated. These include chromosomal translocations in patients with NSCLP, growth factor genes, metalloproteinase (MMP) and transcription factor (patterning) genes, including those in the WNT family. Here, we present results from screening the 10p13 chromosomal translocation region associated with NSCLP, MMP genes clustered on chromosomes 1p36, 11q22.3, 16p13.3, and 16q12-13, and the region containing the WNT5A gene on chromosome 3p21. Markers from three of the regions, 10p13, 16p13.3 (MMP25), and 3p21.2, yielded findings that are sufficiently significant to warrant closer investigation.