This study will focus on additional clinical symptoms in a small selected cohort of CNVs. The chromosomal region chosen, more distal of the 16p11.2 locus, is between BP2 and BP3, a second less frequent non-overlapping recurrent CNV encompassing nine genes including SH2B1 (28.73-28.9 Mb). (16) Bokuchova et al have reported an association between deletions encompassing this gene and severe early onset obesity, as well as insulin resistance. SH2B1 is known to modulate the signaling of ligands to JAK- associates cytokine receptors including insulin and leptin but also growth hormone (GH), and nerve growth factors (NGF). (17, 18)
In this research we will concentrate on the CNVs encompassing SH2B1 and build a clinical score, including: malformations, psychiatric diseases, anthropometric features, epileptic seizures, developmental delay and more, in order to analyze the clinical manifestations of a deletion or a duplication of this region and try to find gender differences in clinical phenotypes explaining a « female protective model ».