Abstract
Intellectual disability (ID) is characterized by limitation in intellectual function and adaptive behavior, with onset in childhood. Frequent identifiable causes of ID originate from chromosomal imbalances. During the last years, array-CGH has successfully contributed to improve the diagnostic detection rate of genetic abnormalities in patients with ID. Most array-CGH studies focused on patients with moderate or severe intellectual disability. Studies on genetic etiology in children with mild intellectual disability (ID) are very rare. We performed array-CGH analysis in 66 children with mild intellectual disability assessed in a population-based study and for whom no genetic etiology was identified. We found one or more copy number variations (CNVs) in 20 out of 66 (~30 %) patients with a mild ID. In eight of them (~12 %), the CNVs were certainly responsible for the phenotype and in six they were potentially pathogenic for ID. Altogether, array-CGH helped to determine the etiology of ID in 14 patients (~21 %). Conclusion: Our results underscore the clinical relevance of array-CGH to investigate the etiology of isolated idiopathic mild ID in patients or associated with even subtle dysmorphic features or congenital malformations.
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Abbreviations
- AAIDD:
-
American Association on Intellectual and Developmental Disabilities
- AGTR2 :
-
Angiotensin II receptor, type 2
- ARHGAP24 :
-
Rho GTPase activating protein 24
- CDH13 :
-
Cadherin 13
- CGH:
-
Comparative genomic hybridization
- CNV:
-
Copy number variations
- DECIPHER:
-
Database of Chromosomal Imbalance and Phenotype in Humans Using Ensembl Resources
- DGV:
-
Database of genomic variants
- EEG:
-
Electroencephalogram
- FISH:
-
Fluorescence in situ hybridization
- GPR87 :
-
G protein-coupled receptor 87
- HEPACAM :
-
Hepatic and glial cell adhesion molecule
- ID:
-
Intellectual disability
- IQ:
-
Intelligence quotient
- K-ABC:
-
Kaufman Assessment Battery for Children
- MDPH:
-
Maison Départementale des Personnes Handicapées
- MED12L :
-
Mediator complex subunit 12-like
- MED12 :
-
Mediator complex subunit 12
- MED13 :
-
Mediator complex subunit 13
- MED13L :
-
Mediator complex subunit 13-like
- MED17 :
-
Mediator complex subunit 17
- MED23 :
-
Mediator complex subunit 23
- MLPA:
-
Multiplex ligation-dependent probe amplification
- NCBI:
-
National center for biotechnology information
- OCRL :
-
Oculocerebrorenal syndrome of Lowe
- OMIM:
-
Online Mendelian Inheritance in Man
- P2RY :
-
Purinergic receptor P2Y
- P2RY12 :
-
Purinergic receptor P2Y, G-protein coupled, 12
- P2RY13 :
-
Purinergic receptor P2Y, G-protein coupled, 13
- P2RY14 :
-
Purinergic receptor P2Y, G-protein coupled, 114
- RHEOP:
-
Registre du Handicap Et Observatoire Périnatal
- TMEM130 :
-
Transmembrane protein 130
- TRRAP :
-
Transformation/transcription domain-associated protein
- UCSC:
-
University of California, Santa Cruz
- VUS:
-
Variant of unknown significance
- WISC:
-
Wechsler Intelligence Scale for Children
- WPPSI-R:
-
Wechsler Preschool and Primary Scale of Intelligence Revised
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We thank family members for their interest and cooperation. This study was supported by grants from the French Ministry (DHOS).
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Coutton, C., Dieterich, K., Satre, V. et al. Array-CGH in children with mild intellectual disability: a population-based study. Eur J Pediatr 174, 75–83 (2015). https://doi.org/10.1007/s00431-014-2367-6
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DOI: https://doi.org/10.1007/s00431-014-2367-6