A single gene defect causing claustrophobia

作者：El Kordi A; Kaestner A; Grube S; Klugmann M; Begemann M; Sperling S; Hammerschmidt K; Hammer C; Stepniak B; Patzig J; De Monasterio Schrader P; Strenzke N; Fluegge G; Werner H B; Pawlak R; Nave K A; Ehrenreich H^*

来源：Translational Psychiatry, 2013, 3: e254.

DOI：10.1038/tp.2013.28

• chromosome 4
• GPM6A
• human pedigree
• miR124
• mouse mutant
• panic disorder

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%26apos;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.

• 出版日期2013-4