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Clinical Journal of Pain:
doi: 10.1097/AJP.0000000000000075
Original Article: PDF Only

Molecular Analysis of Cluster Headache.

Zarrilli, Federica ScD, PhD; Tomaiuolo, Rossella MD, PhD; Ceglia, Carlo ScD, PhD; Lombardo, Barbara ScD, PhD; Izzo, Barbara ScD, PhD; Castaldo, Giuseppe MD, PhD; Pastore, Lucio MD, PhD; De Simone, Roberto MD

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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

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