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.
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.
Yoshiura
K
K
Department of Pediatrics, University of Iowa, Iowa City, Iowa, 52242, USA.
Machida
J
J
Daack-Hirsch
S
S
Patil
S R
SR
Ashworth
L K
LK
Hecht
J T
JT
Murray
J C
JC
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000235:genetics; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D010375:Pedigree; D012333:RNA, Messenger / Q000235:genetics; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D014178:Translocation, Genetic / Q000235:genetics*
C116466:CLPTM1 protein, human; D017931:DNA Primers; D008565:Membrane Proteins; D012333:RNA, Messenger