Characterization of a novel gene disrupted by a balanced chromosomal translocation t(2;19)(q11.2;q13.3) in a family with cleft lip and palate

Genomics. 1998 Dec 1;54(2):231-40. doi: 10.1006/geno.1998.5577.


Cleft lip with or without cleft palate is a common birth defect that is genetically complex. The nonsyndromic forms have been studied genetically using linkage and candidate-gene association studies with only partial success in defining the loci responsible for orofacial clefting. Loci for nonsyndromic cases have been suggested on 2p13, 4q31, 6p24, 17q21-q24, and 19q13.2. Recently, we identified a family in which cleft lip and palate segregated in two of three generations with a balanced chromosomal translocation t(2;19)(q11. 2;q13.3). We used a positional-cloning strategy to identify a novel gene disrupted by the translocation on chromosome 19. Eight rare (q < 0.01) and nine common (q > 0.01) variants of this gene were detected in the DNA of 74 unrelated cases of cleft lip and/or cleft palate; no variants associated significantly with clefting, suggesting that this gene is not a major contributor to abnormal craniofacial development. This gene, CLPTM1, was ubiquitously expressed on Northern blots containing RNA from adult tissues and in whole-mount in situ hybridization of day 10 to 12 mouse embryos. CLPTM1 encodes a transmembrane protein and has strong homology to two Caenorhabditis elegans genes, suggesting that CLPTM1 may belong to a new gene family.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Caenorhabditis elegans / genetics
  • Chromosome Mapping
  • Chromosomes, Human, Pair 19 / genetics*
  • Chromosomes, Human, Pair 2 / genetics
  • Cleft Lip / genetics*
  • Cleft Palate / genetics*
  • Cloning, Molecular
  • DNA Primers / genetics
  • Humans
  • Membrane Proteins / genetics*
  • Mice
  • Molecular Sequence Data
  • Pedigree
  • RNA, Messenger / genetics
  • Sequence Alignment
  • Sequence Analysis, DNA
  • Translocation, Genetic / genetics*


  • CLPTM1 protein, human
  • DNA Primers
  • Membrane Proteins
  • RNA, Messenger

Associated data

  • GENBANK/AF037338
  • GENBANK/AF037339