De novo interstitial deletion of 1q32.2-q32.3 including the entire IRF6 gene in a patient with oral cleft and other dysmorphic features.

BACKGROUND: Microdeletion of the Van der Woude syndrome (VWS) critical region is a relatively rare event, and only a few cases have been reported in the medical literature. The extent of the deletion and the genotype-phenotype correlation are 2 crucial issues.

METHODS AND RESULTS: During analysis of the VWS critical region in 95 families with an isolated cleft of the lip with or without cleft palate, we found a de novo interstitial deletion of 1q32.2-q32.3 in a patient with cleft lip and other dysmorphic features. The present case showed new proximal and distal end breakpoints compared to those previously reported. The results of a short tandem repeat analysis was confirmed using high resolution array-based comparative genomic hybridization and showed an interstitial deletion of approximately 2.98 Mb which involved 25 genes, including the entire IRF6 gene. Direct sequencing of the non-deleted allele of the IRF6 gene did not show any mutation, which supports a haploinsufficiency mechanism of the IRF6 gene in the development of the oral cleft.

CONCLUSION: The present report adds to the collective knowledge that oral cleft is a major clinical feature of the 1q32.2-q32.3 deletion.