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Array-CGH in children with mild intellectual disability: a population-based study

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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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Acknowledgments

We thank family members for their interest and cooperation. This study was supported by grants from the French Ministry (DHOS).

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Correspondence to Charles Coutton.

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Communicated by Beat Steinmann

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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

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