A single gene defect causing claustrophobia

Claustrophobia, the well-known fear of being trapped in narrow/closed spaces, is often considered a conditioned response to traumatic experience. Surprisingly, we found that mutations affecting a single gene, encoding a stress-regulated neuronal protein, can cause claustrophobia. Gpm6a-deficient mic...

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Main Authors:	El-Kordi, A, Kästner, A, Grube, S, Klugmann, M, Begemann, M, Sperling, S, Hammerschmidt, K, Hammer, C, Stepniak, B, Patzig, J, de Monasterio-Schrader, P, Strenzke, N, Flügge, G, Werner, H B, Pawlak, R, Nave, K-A, Ehrenreich, H
Format:	Online
Language:	English
Published:	Nature Publishing Group 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3641414/

id	pubmed-3641414
recordtype	oai_dc
spelling	pubmed-36414142013-05-02 A single gene defect causing claustrophobia El-Kordi, A Kästner, A Grube, S Klugmann, M Begemann, M Sperling, S Hammerschmidt, K Hammer, C Stepniak, B Patzig, J de Monasterio-Schrader, P Strenzke, N Flügge, G Werner, H B Pawlak, R Nave, K-A Ehrenreich, H Original Article Claustrophobia, the well-known fear of being trapped in narrow/closed spaces, is often considered a conditioned response to traumatic experience. Surprisingly, we found that mutations affecting a single gene, encoding a stress-regulated neuronal protein, can cause claustrophobia. Gpm6a-deficient mice develop normally and lack obvious behavioral abnormalities. However, when mildly stressed by single-housing, these mice develop a striking claustrophobia-like phenotype, which is not inducible in wild-type controls, even by severe stress. The human GPM6A gene is located on chromosome 4q32-q34, a region linked to panic disorder. Sequence analysis of 115 claustrophobic and non-claustrophobic subjects identified nine variants in the noncoding region of the gene that are more frequent in affected individuals (P=0.028). One variant in the 3′untranslated region was linked to claustrophobia in two small pedigrees. This mutant mRNA is functional but cannot be silenced by neuronal miR124 derived itself from a stress-regulated transcript. We suggest that loosing dynamic regulation of neuronal GPM6A expression poses a genetic risk for claustrophobia. Nature Publishing Group 2013-04 2013-04-30 /pmc/articles/PMC3641414/ /pubmed/23632458 http://dx.doi.org/10.1038/tp.2013.28 Text en Copyright © 2013 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-sa/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	El-Kordi, A Kästner, A Grube, S Klugmann, M Begemann, M Sperling, S Hammerschmidt, K Hammer, C Stepniak, B Patzig, J de Monasterio-Schrader, P Strenzke, N Flügge, G Werner, H B Pawlak, R Nave, K-A Ehrenreich, H
spellingShingle	El-Kordi, A Kästner, A Grube, S Klugmann, M Begemann, M Sperling, S Hammerschmidt, K Hammer, C Stepniak, B Patzig, J de Monasterio-Schrader, P Strenzke, N Flügge, G Werner, H B Pawlak, R Nave, K-A Ehrenreich, H A single gene defect causing claustrophobia
author_facet	El-Kordi, A Kästner, A Grube, S Klugmann, M Begemann, M Sperling, S Hammerschmidt, K Hammer, C Stepniak, B Patzig, J de Monasterio-Schrader, P Strenzke, N Flügge, G Werner, H B Pawlak, R Nave, K-A Ehrenreich, H
author_sort	El-Kordi, A
title	A single gene defect causing claustrophobia
title_short	A single gene defect causing claustrophobia
title_full	A single gene defect causing claustrophobia
title_fullStr	A single gene defect causing claustrophobia
title_full_unstemmed	A single gene defect causing claustrophobia
title_sort	single gene defect causing claustrophobia
description	Claustrophobia, the well-known fear of being trapped in narrow/closed spaces, is often considered a conditioned response to traumatic experience. Surprisingly, we found that mutations affecting a single gene, encoding a stress-regulated neuronal protein, can cause claustrophobia. Gpm6a-deficient mice develop normally and lack obvious behavioral abnormalities. However, when mildly stressed by single-housing, these mice develop a striking claustrophobia-like phenotype, which is not inducible in wild-type controls, even by severe stress. The human GPM6A gene is located on chromosome 4q32-q34, a region linked to panic disorder. Sequence analysis of 115 claustrophobic and non-claustrophobic subjects identified nine variants in the noncoding region of the gene that are more frequent in affected individuals (P=0.028). One variant in the 3′untranslated region was linked to claustrophobia in two small pedigrees. This mutant mRNA is functional but cannot be silenced by neuronal miR124 derived itself from a stress-regulated transcript. We suggest that loosing dynamic regulation of neuronal GPM6A expression poses a genetic risk for claustrophobia.
publisher	Nature Publishing Group
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3641414/
_version_	1611974235184431104

A single gene defect causing claustrophobia

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