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

TL;DR

This study identifies a new critical region on chromosome 12p linked to specific genetic disorders and suggests how different deletions affect clinical severity.

Contribution

The study defines a revised minimal critical region for 12p deletions and highlights new candidate genes for skeletal and neurodevelopmental issues.

Findings

A revised minimal critical region for 12p deletions was identified through analysis of 22 cases.

Genes like PTHLH, CCDC91, and PPFIBP1 are suggested to contribute to skeletal and neurodevelopmental disorders.

Clinical severity varies depending on the specific cytoband affected, with milder effects at 12p11.

Abstract

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.

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