Physical and transcriptional mapping of the X-linked cleft palate and ankyloglossia (CPX) critical region

Cleft palate most commonly occurs as a sporadic multifactorial disorder wit h a clear but difficult to define genetic component. As a semi-dominant dis order, X-linked cleft palate (CPX) provides a useful model to investigate a congenital defect that is little influenced by non-genetic factors. By usi ng an Icelandic kindred, CPX has been localised between DXS1196 and DXS1217 and mapped, in a 3-Mb yeast artificial chromosome contig, at Xq21.3. Marke rs generated from this physical map have now been used to construct a conti g of PI and bacterial artificial chromosome clones for genomic DNA sequenci ng. Genomic DNA sequence analysis has revealed two novel expressed genes an d two pseudogenes in the order Cen-KLHL4-LAMRL5-CAPZA1P-CPXCR1-Tel. KLHL4 a nd CPXCR1 are widely expressed in fetal tissues, including the tongue, mand ible and palate. DNA mutation screening of CPXCR1 has revealed several sequ ence variants present on all affected CPX chromosomes. However, these varia nts have also been detected at a lower frequency on unaffected chromosomes, indicating that they are polymorphisms that are unlikely to cause the CPX phenotype.