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J Pediatr. 2017 Jun;185:160-166.e1. doi: 10.1016/j.jpeds.2017.02.023. Epub 2017 Mar 8.

Copy Number Variations Found in Patients with a Corpus Callosum Abnormality and Intellectual Disability.

Author information

1
APHP, GH Pitié Salpêtrière, Department of genetics, unit of medical genetics, reference center for intellectual disabilities of rare causes, Paris, France; GRC Intellectual Disability and Autism, UPMC, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, Inserm U 1127, CNRS UMR 7225, ICM, Paris, France. Electronic address: solveig.heide@aphp.fr.
2
APHP, GH Pitié-Salpêtrière, Department of genetics, unit of developmental genomic, Paris, France.
3
APHP, Hôpital Armand-Trousseau, Division of pediatric neurology, Paris, France; GRC ConCer-LD, UPMC, Paris, France; Inserm U1141, Paris, France.
4
APHP, Hôpital Armand-Trousseau, Department of genetics, division of chromosomal genetics, Paris, France.
5
Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, Inserm U 1127, CNRS UMR 7225, ICM, Paris, France; APHP, GH Pitié-Salpêtrière, Department of genetics, unit of developmental genomic, Paris, France; Department of translational medicine and neurogenetics, IGBMC, CNRS UMR 7104/INSERM U964, Université de Strasbourg, Illkirch, France; Institute of medical genetics of Alsace, Division of cytogenetics, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
6
Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, Inserm U 1127, CNRS UMR 7225, ICM, Paris, France; APHP, GH Pitié-Salpêtrière, Department of genetics, unit of developmental genomic, Paris, France.
7
APHP, GH Pitié Salpêtrière, Department of genetics, unit of medical genetics, reference center for intellectual disabilities of rare causes, Paris, France.
8
APHP, Hôpital Armand-Trousseau, Department of genetics, Division of clinical genetics, Paris, France.
9
CHU Bordeaux, Division of medical genetics, INSERM U1211, Université de Bordeaux, Bordeaux, France.
10
Hôpital Bretonneau, CHU Tours, Division of genetics, Tours, France.
11
CHU Nantes, Institute of biology, Division of medical genetics, Inserm UMR 915/CNRS ERL3147, Nantes, France.
12
APHP, Hôpital Robert-Debré, Division of medical genetics, Paris, France.
13
CHU Dijon, Hôpital d'enfants, FHU-TRANSLAD, Genetic Center, Dijon, France.
14
HCL, GH Est, Division of pediatric neurology, Bron, France.
15
HCL, Division of genetics, Bron, France; Center of Research in neurosciences of Lyon, Inserm U1028, UMR CNRS 5292, GENDEV Team, Université Claude BernardLyon 1, Lyon, France.
16
APHP, GH Pitié Salpêtrière, Department of genetics, unit of medical genetics, reference center for intellectual disabilities of rare causes, Paris, France; GRC Intellectual Disability and Autism, UPMC, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, Inserm U 1127, CNRS UMR 7225, ICM, Paris, France; APHP, Hôpital Armand-Trousseau, Department of genetics, Division of clinical genetics, Paris, France.

Abstract

OBJECTIVE:

To evaluate the role that chromosomal micro-rearrangements play in patients with both corpus callosum abnormality and intellectual disability, we analyzed copy number variations (CNVs) in patients with corpus callosum abnormality/intellectual disability STUDY DESIGN: We screened 149 patients with corpus callosum abnormality/intellectual disability using Illumina SNP arrays.

RESULTS:

In 20 patients (13%), we have identified at least 1 CNV that likely contributes to corpus callosum abnormality/intellectual disability phenotype. We confirmed that the most common rearrangement in corpus callosum abnormality/intellectual disability is inverted duplication with terminal deletion of the 8p chromosome (3.2%). In addition to the identification of known recurrent CNVs, such as deletions 6qter, 18q21 (including TCF4), 1q43q44, 17p13.3, 14q12, 3q13, 3p26, and 3q26 (including SOX2), our analysis allowed us to refine the 2 known critical regions associated with 8q21.1 deletion and 19p13.1 duplication relevant for corpus callosum abnormality; report a novel 10p12 deletion including ZEB1 recently implicated in corpus callosum abnormality with corneal dystrophy; and) report a novel pathogenic 7q36 duplication encompassing SHH. In addition, 66 variants of unknown significance were identified in 57 patients encompassed candidate genes.

CONCLUSIONS:

Our results confirm the relevance of using microarray analysis as first line test in patients with corpus callosum abnormality/intellectual disability.

KEYWORDS:

CNV; SNP array; agenesis of corpus callosum; chromosomal microarray; corpus callosum; dysgenesis of corpus callosum

Comment in

PMID:
28284480
DOI:
10.1016/j.jpeds.2017.02.023
[Indexed for MEDLINE]

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