title: Mutation analysis of CLPTM 1 and PVRL 1 genes in patients with non-syndromic clefts of lip, alveolus and palate.
abstract: BACKGROUND
  Non-syndromic cleft lip with or without cleft palate (CL/P), is one of the most common birth defects, but its aetiology is largely unknown. The aim of this study was to determine the sequence changes of the Cleft Lip and Palate Transmembrane Protein 1 (CLPTM 1) and Poliovirus Receptor Related 1 (PVRL 1) genes in patients with non-syndromic complete clefts of lip, alveolus and palate and to correlate these findings with clinical features.
  
  
  METHODS
  25 patients were analysed (14 male and 11 female, aged 4-10 years) of European descent (9 patients with right, 9 with left and 7 patients with bilateral CLAP) and 25 controls, respectively. Exons 2-14 of the CLPTM1 and exons 1-6 of the PVRL1 gene were analysed by a direct sequencing method using DNA extracted from whole blood.
  
  
  RESULTS
  A novel in frame Glu441-Gly442 ins Glu mutation of the PVRL 1 gene in combination with novel exon mutations Gly331Gly, Ala88Ala, Pro309Pro and intron change IVS7-10G/A of the CLPTM 1 gene were found in 9 patients. The Glu441-Gly442 ins Glu mutation and the intron change IVS7-10G/A were not detected in 25 controls.
  
  
  CONCLUSIONS
  These results suggest that a simultaneous occurrence of PVRL1 and CLPTM 1 gene mutations in cleft patients does not correlate with the type of cleft (left, right, bilateral) or the gender of the patients. If a combination of the intron change IVS7-10G/A, exon changes Gly331Gly, Ala88Ala and Pro309Pro of the CLMPT 1 gene and Glu441-Gly442 ins Glu mutation of the PVRL 1 gene could be a genetic factor for non-syndromic clefts of the primary and the secondary palates, it is important to investigate more patients and controls.
authors.affiliation: Department of Cranio-Maxillofacial and Oral Surgery, Hospital of Cranio-Maxillofacial and Oral Surgery, Medical University of Vienna, Austria. dritan.turhani@meduniwien.ac.at
authors.forename: Dritan
authors.initials: D
authors.lastname: Turhani
authors.forename: Chike B
authors.initials: CB
authors.lastname: Item
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Watzinger
authors.forename: Klaus
authors.initials: K
authors.lastname: Sinko
authors.forename: Franz
authors.initials: F
authors.lastname: Watzinger
authors.forename: Guenter
authors.initials: G
authors.lastname: Lauer
authors.forename: Rolf
authors.initials: R
authors.lastname: Ewers
mesh_terms: D000409:Alanine / Q000235:genetics; D000539:Alveolar Process / Q000002:abnormalities; D015815:Cell Adhesion Molecules / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D018698:Glutamic Acid / Q000235:genetics; D005998:Glycine / Q000235:genetics; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics*; D007438:Introns / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D000075983:Nectins; D011392:Proline / Q000235:genetics; D011991:Receptors, Virus / Q000235:genetics*; D020539:Sequence Analysis, Protein / Q000379:methods; D012737:Sex Factors
chemical_list: C116466:CLPTM1 protein, human; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D008565:Membrane Proteins; C000619010:NECTIN1 protein, human; D000075983:Nectins; D011991:Receptors, Virus; D018698:Glutamic Acid; D011392:Proline; D000409:Alanine; D005998:Glycine