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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

1
Inserm U1079, Institute for Research and Innovation in Biomedicine, University of Rouen, France.
2
Inserm U1130, Neuroscience Paris Seine, Paris, France.
3
CNRS UMR 8246, Neuroscience Paris Seine, Paris, France.
4
Sorbonne Universités, UPMC Univ Paris 6, Institut de Biologie Paris-Seine, Paris, France.
5
The Centre for Applied Genomics, and Program in Genetics and Genome Biology, the Hospital for Sick Children, Toronto, Ontario, Canada.
6
Population Diagnostics, Inc., Melville, New York.
7
Unité de neuropédiatrie et pathologie du développement, CHU Paris Est-Hôpital d'Enfants Armand-Trousseau, Paris, France.
8
Service de génétique médicale, CHU de Poitiers, France.
9
McLaughlin Centre and Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
10
Centre Hospitalier du Rouvray, Sotteville-lès-Rouen, France.

Abstract

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.

KEYWORDS:

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

PMID:
26978485
DOI:
10.1002/ajmg.b.32416
[Indexed for MEDLINE]
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