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Fraternal twins with autism, severe cognitive deficit, and epilepsy: diagnostic role of chromosomal microarray analysis
Journal article   Peer reviewed

Fraternal twins with autism, severe cognitive deficit, and epilepsy: diagnostic role of chromosomal microarray analysis

Jaime Imitola, Diana Walleigh, Carol E Anderson, Reena Jethva, Karen S Carvalho, Agustin Legido and Divya S Khurana
Seminars in pediatric neurology, v 21(2), pp 167-171
Jun 2014
DOI: https://doi.org/10.1016/j.spen.2014.04.027
PMID: 25149956
Featured in Collection :   UN Sustainable Development Goals @ Drexel

Abstract

Autistic Disorder - diagnosis Autistic Disorder - genetics Autistic Disorder - physiopathology Brain - physiopathology Cell Adhesion Molecules, Neuronal - genetics Child Cognition Disorders - diagnosis Cognition Disorders - genetics Cognition Disorders - physiopathology Diagnosis, Differential Electroencephalography Epilepsy, Absence - diagnosis Epilepsy, Absence - genetics Epilepsy, Absence - physiopathology Female Humans Male Microarray Analysis - methods Nerve Tissue Proteins - genetics Sequence Deletion Twins, Dizygotic
A 7-year-old child presented with atypical absence epilepsy. He also had autism and severe cognitive deficit. As part of his diagnostic workup, a chromosomal microarray analysis was performed, which showed novel biallelic deletions in the neurexin 1 gene (NRXN1). His fraternal twin sister, who also had autism and cognitive impairment, was subsequently found to have the same biallelic deletions. Deletions included a 272-282kb loss at band 2p16.3 in one allele and a smaller 135-174-kb loss on the second allele. Neurexin 1 (NRXN1) is a cell adhesion protein, forming a synaptic complex with neuroligin. This signals a pathway that is critical for activity-dependent synaptic transmission. Mutations in this gene have been associated with autism and neurodevelopmental delay. Although there are many reports of heterozygous mutations with variable expressivity, only 3 cases with biallelic NRXN1 mutations have been previously reported, all of which have a more severe phenotype. We report 2 siblings with biallelic deletions, both of which affect the promoter region and exons 1-5 in the α-NRXN1 isoform, which has a role in the Ca(2+)-dependent release of neurotransmitters in the central nervous system. Our cases expand the phenotype of biallelic α NRXN 1 mutations and emphasize the important role of NRXN1 in autism and intellectual disability. Chromosomal microarray analysis should be the clinical standard in all specialties for first-tier genetic testing in autistic spectrum disorders.

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Web of Science research areas
Clinical Neurology
Pediatrics
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