Abstract
Variable clinical presentations of patients with chromosomally detected deletions in the distal long arm (q) of chromosome 4 have been reported. The lack of molecular characterization of the deletion sizes and deleted genes hinders further genotypeβphenotype correlation. Using a validated oligonucleotide array comparative genomic hybridization (oaCGH) analysis, we examined two patients with apparent chromosomal deletions in the distal 4q region. In the first, oaCGH identified a 2.441 megabase (Mb) duplication and a 12.651βMb deletion at 4q34.1 in a pregnant female who transmitted this aberration to her son. This mother has only learning disabilities while her son had both renal and cardiac anomalies in the newborn period. Unrecognized paternal genetic factors may contribute to the variable expression. The second patient is a 17βyearβold female with a history of Pierre Robin sequence, cardiac abnormalities and learning disabilities. She was diagnosed prenatally with a de novo 4q deletion, and oaCGH defined a 16.435βMb deletion of 4q34.1β4q35.2. Phenotypic comparison and subtractive genomic mapping between these two cases suggested a 4βMb region possibly harboring a candidate gene for Pierre Robin sequence. Our cases and review of reported cases with genomic findings indicated the presence of familial variants with variable expressivity as well as de novo or inherited pathogenic simple deletion, duplication and complex deletion and duplication in the distal 4q region. Β© 2009 WileyβLiss, Inc.