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Chromosomal loss of 3q26.3-3q26.32, involving a partial neuroligin 1 deletion, identified by genomic microarray in a child with microcephaly, seizure disorder, and severe intellectual disability

Authors

  • Alison Millson,

    Corresponding author
    1. ARUP Institute for Clinical and Experimental Pathology, ARUP Laboratories, Salt Lake City, Utah
    • ARUP Laboratories, 500 Chipeta Way, Salt Lake City, UT 84108.
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  • Danielle LaGrave,

    1. Cytogenetics and Molecular Cytogenetics, ARUP Laboratories, Salt Lake City, Utah
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  • Mary J.H. Willis,

    1. Clinical Genetics, Naval Medical Center, San Diego, California
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  • Leslie R. Rowe,

    1. ARUP Institute for Clinical and Experimental Pathology, ARUP Laboratories, Salt Lake City, Utah
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  • Elaine Lyon,

    1. ARUP Institute for Clinical and Experimental Pathology, ARUP Laboratories, Salt Lake City, Utah
    2. Department of Pathology, University of Utah, Salt Lake City, Utah
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  • Sarah T. South

    1. ARUP Institute for Clinical and Experimental Pathology, ARUP Laboratories, Salt Lake City, Utah
    2. Cytogenetics and Molecular Cytogenetics, ARUP Laboratories, Salt Lake City, Utah
    3. Department of Pediatrics, University of Utah, Salt Lake City, Utah
    4. Department of Pathology, University of Utah, Salt Lake City, Utah
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  • How to cite this article: Millson A, LaGrave D, Willis MJH, Rowe LR, Lyon E, South ST. 2012. Chromosomal loss of 3q26.3-3q26.32, involving a partial neuroligin 1 deletion, identified by genomic microarray in a child with microcephaly, seizure disorder, and severe intellectual disability. Am J Med Genet Part A 158A:159–165.

  • The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, or the United States Government.

Abstract

Neuroligin 1 (NLGN1) is one of five members of the neuroligin gene family and may represent a candidate gene for neurological disorders, as members of this family are involved in formation and remodeling of central nervous system synapses. NLGN1 is expressed predominantly in the central nervous system, where it dimerizes and then binds with β-neurexin to form a functional synapse. Mutations in neurexin 1 (NRXN1) as well as two other members of the neuroligin family, NLGN3 and NLGN4, have been associated with autism and mutations in NLGN4 have also been associated with intellectual disability, seizures, and EEG abnormalities. Genomic microarray is recommended for the detection of chromosomal gains or losses in patients with intellectual disability and multiple congenital anomalies. Results of uncertain significance are not uncommon. Parental studies can provide additional information by demonstrating that the imbalance is either de novo or inherited, and therefore is more or less likely to be causative of the clinical phenotype. However, the possibility that even inherited deletions and duplications may play a role in the phenotype of the proband cannot be excluded as many copy number variants associated with neurodevelopmental conditions show incomplete penetrance and may be inherited from an unaffected parent. Here, we report on a patient with a 2.2 Mb deletion at 3q26.3-3q26.32—encompassing the terminal end of NLGN1 and the entire NAALADL2 gene—detected by genomic microarray, and confirmed by FISH and real-time quantitative PCR. The same size deletion was subsequently found in her healthy, asymptomatic, adult mother. © 2011 Wiley Periodicals, Inc.

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