Objectives: Cluster headache (CH) is characterized by severe, recurrent, unilateral attacks of extreme intensity and brief duration. Variants in a myriad of genes were studied in sporadic CH patients, often with conflicting results.
Methods: We studied gene mutations in some candidate genes, i.e., hypocretin-receptor 2, Clock and alcohol-dehydrogenase (ADH) 4 in 54 unrelated sporadic CH subjects and in 200 controls and, for the first time, in 8 kindreds/families that included more affected and non-affected cases. Furthermore, we performed the whole genome scanning by comparative genomic hybridization (CGH), searching for rearrangements associated to DNA gain or loss in a subset of sporadic and familial CH and control subjects.
Results: The analysis of candidate genes revealed that only allele and genotype frequency of the two ADH4 mutations resulted significantly between sporadic CH and controls; the same mutations were homozygous in CH patients from two families. The CGH analysis revealed two novel rearrangements that involved the intron regions of thyrotropin-releasing hormone degrading enzyme and neurexin (NRXN) 3 genes, respectively. The first one was present either in CH and in control subjects; the second was specifically found in some sporadic and familial CH cases.
Conclusions: our data (although obtained on a small number of cases) confirm the genetic heterogeneity of CH suggesting that mutations in the ADH4 gene and a novel rearrangement involving neurexin 3 gene might be related to CH in a subset of cases.
(C) 2014 by Lippincott Williams & Wilkins