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A de novo t(10;19)(q22.3;q13.33) leads to ZMIZ1/PRR12 reciprocal fusion transcripts in a girl with intellectual disability and neuropsychiatric alterations

Overview of attention for article published in neurogenetics, July 2015
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Title
A de novo t(10;19)(q22.3;q13.33) leads to ZMIZ1/PRR12 reciprocal fusion transcripts in a girl with intellectual disability and neuropsychiatric alterations
Published in
neurogenetics, July 2015
DOI 10.1007/s10048-015-0452-2
Pubmed ID
Authors

Carlos Córdova-Fletes, Ma. Guadalupe Domínguez, Ilse Delint-Ramirez, Herminia G. Martínez-Rodríguez, Ana María Rivas-Estilla, Patricio Barros-Núñez, Rocío Ortiz-López, Vivian Alejandra Neira

Abstract

We report a girl with intellectual disability (ID), neuropsychiatric alterations, and a de novo balanced t(10;19)(q22.3;q13.33) translocation. After chromosome sorting, fine mapping of breakpoints by array painting disclosed disruptions of the zinc finger, MIZ-type containing 1 (ZMIZ1) (on chr10) and proline-rich 12 (PRR12) (on chr19) genes. cDNA analyses revealed that the translocation resulted in gene fusions. The resulting hybrid transcripts predict mRNA decay or, if translated, formation of truncated proteins, both due to frameshifts that introduced premature stop codons. Though other molecular mechanisms may be operating, these results suggest that haploinsufficiency of one or both genes accounts for the patient's phenotype. ZMIZ1 is highly expressed in the brain, and its protein product appears to interact with neuron-specific chromatin remodeling complex (nBAF) and activator protein 1 (AP-1) complexes which play a role regulating the activity of genes essential for normal synapse and dendrite growth/behavior. Strikingly, the patient's phenotype overlaps with phenotypes caused by mutations in SMARCA4 (BRG1), an nBAF subunit presumably interacting with ZMIZ1 in brain cells as suggested by our results of coimmunoprecipitation in the mouse brain. PRR12 is also expressed in the brain, and its protein product possesses domains and residues thought to be related in formation of large protein complexes and chromatin remodeling. Our observation from E15 mouse brain cells that a Prr12 isoform was confined to nucleus suggests a role as a transcription nuclear cofactor likely involved in neuronal development. Moreover, a pilot transcriptome analysis from t(10;19) lymphoblastoid cell line suggests dysregulation of genes linked to neurodevelopment processes/neuronal communication (e.g., NRCAM) most likely induced by altered PRR12. This case represents the first constitutional balanced translocation disrupting and fusing both genes and provides clues for the potential function and effects of these in the central nervous system.

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Mendeley readers

The data shown below were compiled from readership statistics for 23 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 23 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 5 22%
Student > Bachelor 4 17%
Professor 2 9%
Student > Master 2 9%
Unspecified 2 9%
Other 8 35%
Readers by discipline Count As %
Agricultural and Biological Sciences 7 30%
Unspecified 5 22%
Medicine and Dentistry 5 22%
Biochemistry, Genetics and Molecular Biology 2 9%
Psychology 2 9%
Other 2 9%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 15 July 2015.
All research outputs
#9,771,367
of 12,228,633 outputs
Outputs from neurogenetics
#223
of 265 outputs
Outputs of similar age
#163,586
of 234,998 outputs
Outputs of similar age from neurogenetics
#8
of 8 outputs
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