DiGeorge-like syndrome in a child with a 3p12.3 deletion involving miRNA-4273 born to a diabetic mother

INTRODUCTION: Chromosome 22q11.2 deletion is the most commonly chromosomal alteration associated with DiGeorge syndrome (DGS). However, 22q11.2 deletion is not the only underlying cause of DGS. Recently it has been reported that miRNA may modulate the expression of critical T-box transcriptional regulators during midface development and the Bmp-signalling. OBJECTIVE: To describe the immunological and molecular phenotype of a child with DGS-like syndrome born to a diabetic mother. METHODS: Cytogenetic and molecular analysis includes fluorescent in situ hybridization (FISH), Array-CGH and TBX1 sequencing. Lymphocyte subpopulations were studied by flow-cytometry and PBMC proliferation by standard method. RESULTS: a 6-year-old Caucasian male was admitted for thymic aplasia, recurrent airway infections, hypoparathyroidism, renal agenesis, patent oval foramen, septum pellucidum cyst, language delay and dysmorphisms. The immunological evaluation revealed normal serum Ig levels. The immunophenotype revealed a reduction of CD3+ (373cell/mm3), CD4+ (163cells/mm3), CD8+ (388cells/mm3), CD3+CD4+CD45RA (47cells/mm3), CD3+CD4+CD45RO (116cells/mm3) cells. B-lymphocytes were increased (1352cells/mm3), while CD56+ were normal. The proliferative response to PHA and Pockweed was decreased, corresponding to the 45% and 39% of the control, respectively. FISH analysis and TBX1 sequencing were negative. Array CGH revealed a 371Kb-interstitial deletion at 3p12.3 involving the ZNF717, MiRNA-1243 and 4273 genes. Among the MiRNA-4273 predicted target-genes, we found Bone Morphogenetic protein-3 (BMP-3), involved in several steps of embryogenesis, as in kidney and lung organogenesis. CONCLUSIONS: We report on a novel association between a DG-like phenotype and a 3p12.3 chromosomal deletion in an infant born to a diabetic mother, although the causal relationship remains to be proved.