Genetic Dysruption of the Histaminergic Pathways: A Novel Deletion at the 15q21.2 <i>locus</i> Associated with Variable Expressivity of Neuropsychiatric Disorders.

The involvement of the Histaminergic System (HS) in neuropsychiatric disease is not well-documented, and few studies have described patients affected by different neuropsychiatric conditions harbouring disruptions in genes involved in the HS. In humans, histamine is synthetised from histidine by the histidine decarboxylase enzyme encoded by the <i>HDC</i> gene (OMIM*142704). This is the sole enzyme in our organism able to synthetise histamine from histidine. Histamine is also contained in many different food types. We hereby describe a twenty-one-year-old female diagnosed with a borderline intellectual disability with autistic traits and other peculiar neuropsychological features carrying a 175-Kb interstitial deletion on chromosome 15q21.2. The deletion was inherited from the mother, who was affected by a severe anxiety disorder. The deleted region contains entirely the <i>HDC</i> and the <i>SLC27A2</i> genes and partially the <i>ATP8B4</i> gene. The <i>HDC</i> gene has been previously associated with Tourette Syndrome (TS). Based on the functional role of the <i>HDC</i>, we propose this gene as the best candidate to explain many traits associated with the clinical phenotype of our patient and of her mother.