Cardiac malformations are commonly seen in individuals with terminal and interstitial deletions involving chromosome band 7p22. Although these malformations represent a significant cause of morbidity, the dosage-sensitive gene(s) that underlie these defects have yet to be identified. In this report, we describe a 16-month-old male with tetralogy of Fallot, bilateral second branchial arch remnants, and mild dysmorphic features. Array comparative genomic hybridization analysis revealed a less than 400 kb interstitial deletion on chromosome 7p22. The deletion was confirmed by real-time quantitative PCR and FISH analyses and was not detected in samples obtained from the child's parents. Molecular data from this de novo deletion, in combination with data from other isolated 7p deletions in the literature, can be used to define a less than 200 kb minimal deleted region for cardiac malformations on 7p22. This minimal deleted region spans all, or portions, of the coding regions of four known genes-MAD1L1, FTSJ2, NUDT1, and SNX8-and may include upstream regulatory elements of EIF3B. It is likely that one or more of these five genes, alone or in combination, plays an important, yet previously uncharacterized, role in cardiac development.
Copyright © 2011 Wiley-Liss, Inc.