Interstitial 12p Deletion Syndrome: Revised Minimal Critical Region and Review of the Literature

Background: Interstitial deletions of the short arm of chromosome 12 are rare, and very little is known about the potential genetic basis of the most common phenotypic presentations to date described in the literature. Methods: In the present study, we present a new patient carrying a heterozygous de novo 12p deletion, identified by a-CGH. Results: Comparison between the new case with phenotypically similar 12p-deleted patients drawn from the literature and from the DECIPHER (the DatabasE of Chromosomal Imbalances and Phenotypes using Ensembl Resources) database allowed us to analyze 22 cases and to define a revised minimal critical region not previously considered. Discussion: Within the new minimal critical region, we identified genes intolerant to haploinsufficiency, highlighting the involvement of PTHLH and CCDC91 in the onset of skeletal abnormalities and proposing the involvement of PPFIBP1 in neurodevelopmental disorders (although it has previously been associated only with autosomal recessive conditions). Conclusions: We suggest that clinical severity in cases with 12p deletions varies depending on the cytobands involved, being more moderate when they occur at 12p11—where the gene DENND5B (12p11.23) has recently been associated with a dominant neurodevelopmental disorder—than at 12p12.