Send to

Choose Destination
Am J Med Genet B Neuropsychiatr Genet. 2016 Apr;171B(3):377-82. doi: 10.1002/ajmg.b.32416. Epub 2016 Jan 14.

The 22q11 PRODH/DGCR6 deletion is frequent in hyperprolinemic subjects but is not a strong risk factor for ASD.

Author information

Inserm U1079, Institute for Research and Innovation in Biomedicine, University of Rouen, France.
Inserm U1130, Neuroscience Paris Seine, Paris, France.
CNRS UMR 8246, Neuroscience Paris Seine, Paris, France.
Sorbonne Universités, UPMC Univ Paris 6, Institut de Biologie Paris-Seine, Paris, France.
The Centre for Applied Genomics, and Program in Genetics and Genome Biology, the Hospital for Sick Children, Toronto, Ontario, Canada.
Population Diagnostics, Inc., Melville, New York.
Unité de neuropédiatrie et pathologie du développement, CHU Paris Est-Hôpital d'Enfants Armand-Trousseau, Paris, France.
Service de génétique médicale, CHU de Poitiers, France.
McLaughlin Centre and Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
Centre Hospitalier du Rouvray, Sotteville-lès-Rouen, France.


The proline dehydrogenase (PRODH) gene maps to 22q11.2 in the region deleted in the velo-cardio-facial syndrome (VCFS). A moderate to severe reduction (>50%) in PRODH activity resulting from recessive deletions and/or missense mutations has been shown to cause type 1 hyperprolinemia (HPI). Autistic features have been reported as a common clinical manifestation of HPI. Here we studied the frequency of a recurrent small 22q11.2 deletion encompassing PRODH and the neighboring DGCR6 gene in three case-control studies, one comprising HPI patients (n = 83), and the other two comprising autism spectrum disorder (ASD) patients (total of n = 2800), analyzed with high-resolution microarrays. We found that the PRODH deletion is a strong risk factor for HPI (OR = 50.7; 95%CI = 7.5-2147) but not for ASD (P = 0.4, OR = 0.6-3.3). This result indicates either that the suggested association between ASD and HPI is spurious and results from a bias leading to the preferential inclusion of patients with autistic features in HPI series, or that HPI is present in only a very small subset of ASD patients. In this latter case, a very large sample size would be required to detect an association between the PRODH deletion and ASD in a case-control study.


22q11.2 deletion; autism; copy number variant; hyperprolinemia; proline dehydrogenase

[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Wiley Icon for HAL archives ouvertes
Loading ...
Support Center