Novel cleft susceptibility genes in chromosome 6q

J Dent Res. 2010 Sep;89(9):927-32. doi: 10.1177/0022034510370004. Epub 2010 May 28.


Cleft lip/palate is a defect of craniofacial development. In previous reports, chromosome 6q has been suggested as a candidate region for cleft lip/palate. A multipoint posterior probability of linkage analysis of multiplex families from the Philippines attributed an 88% probability of harboring a cleft-susceptibility gene to a narrower region on bands 6q14.2-14.3. We genotyped 2732 individuals from families and unrelated individuals with and without clefts to investigate the existence of possible cleft-susceptibility genes in this region. We found association of PRSS35 and SNAP91 genes with cleft lip/palate in the case-control cohort and in Caucasian families. Haplotype analyses support the individual associations with PRSS35. We found Prss35 expression in the head and palate of mouse embryos at critical stages for palatogenesis, whereas Snap91 was expressed in the adult brain. We provide further evidence of the involvement of chromosome 6q in cleft lip/palate and suggest PRSS35 as a novel candidate gene.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brazil
  • Case-Control Studies
  • Chi-Square Distribution
  • Chromosomes, Human, Pair 6*
  • Cleft Lip / genetics*
  • Cleft Palate / genetics*
  • Databases, Genetic
  • European Continental Ancestry Group / genetics
  • Gene Frequency
  • Genetic Loci
  • Genetic Predisposition to Disease*
  • Haplotypes
  • Humans
  • Linkage Disequilibrium
  • Mice
  • Monomeric Clathrin Assembly Proteins / genetics
  • Palate, Hard / embryology
  • Polymorphism, Single Nucleotide
  • Serine Endopeptidases / genetics
  • Serine Proteases / genetics*


  • Monomeric Clathrin Assembly Proteins
  • clathrin assembly protein AP180
  • PRSS35 protein, human
  • Serine Proteases
  • PRSS35 protein, mouse
  • Serine Endopeptidases

Grant support