Mosaic deletion 11p13 in a child with dopamine beta-hydroxylase deficiency--case report and review of the literature.

Dopamine beta-hydroxylase (DBH) deficiency is characterized by a lack of sympathetic noradrenergic function. Affected individuals exhibit profound deficits in autonomic regulation of cardiovascular function. The diagnosis of DBH deficiency is based on clinical findings, biochemical studies, and sequencing of DBH gene. We report here the characterization of a mosaic cytogenetic abnormality detected by array-CGH in a 16-year-old female with primary DBH deficiency together with dysmorphic features. These features could not be explained by DBH deficiency leading to further investigation. Karyotype was reported normal (46,XX), while a targeted genomic array-CGH revealed a mosaic loss for a segment of at least 1 Mb across 11p13. This segmental loss included the PAX6 and WT1 genes within the WAGR syndrome critical region. Interestingly, the derivative chromosome 11 was observed only in about 28% of cells analyzed. Utilizing a genome-wide oligonucleotide-based array, the deletion segment was estimated to encompass a segment of ∼10 Mb. Mosaic deletions of 11p13 in WAGR are extremely uncommon. In this case it is distinctly possible that the patient's bilateral iris colobomata might be a manifestation, albeit abbreviated, of the haploinsufficiency for PAX6. This case highlights the importance of cytogenetic analysis when a mutation alone cannot account for the complete phenotype. It also emphasizes the enhanced ability of high-resolution array-CGH techniques in accurately detecting subtle rearrangements in a mosaic form. Finally, it demonstrates the possible phenotypic effects of low-level PAX6 haploinsufficiency in a dosage-sensitive manner. © 2010 Wiley-Liss, Inc.