Partial deletion of GLRB and GRIA2 in a patient with intellectual disability

We report about the partial de novo loss of GLRB and GRIA2 in an individual with intellectual disability (ID). No additional mutations were found in either gene. GLRB itself does not seem to be a good candidate as it causes autosomal recessive hyperekplexia and no symptoms were found in the patient....

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Bibliographic Details
Published in:European journal of human genetics : EJHG 2013-01, Vol.21 (1), p.112-114
Main Authors: Hackmann, Karl, Matko, Sarah, Gerlach, Eva-Maria, von der Hagen, Maja, Klink, Barbara, Schrock, Evelin, Rump, Andreas, Di Donato, Nataliya
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Blood
Brain
Child, Preschool
Clonal deletion
Exons
Fusion protein
Gene Fusion
Glutamic acid receptors
Haploinsufficiency
Humans
In Situ Hybridization, Fluorescence
Intellectual disabilities
Intellectual Disability - genetics
Language
Male
Mental retardation
Molecular Sequence Data
Mutation
Open reading frames
Phenotypes
Receptors, AMPA - genetics
Receptors, Glycine - genetics
Sequence Deletion
Short Report
Signal transduction
Splicing
Startle response
Synapses
Transcription
Transduction
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Summary:We report about the partial de novo loss of GLRB and GRIA2 in an individual with intellectual disability (ID). No additional mutations were found in either gene. GLRB itself does not seem to be a good candidate as it causes autosomal recessive hyperekplexia and no symptoms were found in the patient. Mutations of GRIA2 have not been described as cause of ID to date. Nonetheless, it is a very attractive candidate because it encodes a subunit of a glutamate receptor, which is highly expressed in postsynaptic structures and has an important role in signal transduction across synapses. Although we were able to isolate a fragment of a fusion transcript of both genes from the patient's blood, we were not able to isolate a transcript with an open reading frame throughout the entire length. The reading frame could be restored by differential splicing, which might take place in brain tissue but not in blood. We assume that either haploinsufficiency of GRIA2 or a GLRB/GRIA2 fusion gene leading to a protein with dominant-negative properties is causing the phenotype of the patient.
ISSN:1018-4813
1476-5438
DOI:10.1038/ejhg.2012.97