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

Abstract

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 HDC 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 HDC and the SLC27A2 genes and partially the ATP8B4 gene. The HDC gene has been previously associated with Tourette Syndrome (TS). Based on the functional role of the HDC, we propose this gene as the best candidate to explain many traits associated with the clinical phenotype of our patient and of her mother.

Etiology of Borderline Intellectual Functioning

“…SNAP-25 polymorphism has been linked to intelligence through the mediating role of brain morphological features among children with BIF [ 15 ]. Additionally, case reports of BIF have observed genetic mutations in loci, including 7q11.23 [ 16 ] and 15q21.2 [ 17 ], and genes such as CACNA1I [ 18 ], USP7 [ 19 ], LRFN2 [ 20 ], and MAGEL2 [ 21 ]. However, whether these genetic variants are specifically related to BIF or overall brain development is unclear and requires further research.…”