Molecular Analysis of Cluster Headache. Issue 1 (January 2015)

• Record Type: Journal Article
• Authors: Zarrilli, Federica; Tomaiuolo, Rossella; Ceglia, Carlo; Lombardo, Barbara; Izzo, Barbara; Castaldo, Giuseppe; Pastore, Lucio; De Simone, Roberto
• Is Part Of: Clinical journal of pain. Volume 31:Issue 1(2015)
• Publication Date: 2015-01
• Subjects: CH -- cluster headache -- genetics -- gene mutations -- CGH; Pain -- Periodicals; Pain -- Treatment -- Periodicals; Analgesia -- Periodicals; 616.047205
• DOI: 10.1097/AJP.0000000000000075
• Languages: English
• ISSNs: 0749-8047

Abstract

Abstract : 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, hypocretin receptor 2, Clock, and alcohol dehydrogenase 4 ( ADH4 ), in 54 unrelated sporadic CH patients and in 200 controls in 8 kindreds/families that included more affected and nonaffected cases. Furthermore, we performed the whole-genome scanning by comparative genomic hybridization, searching for rearrangements associated with DNA gain or loss in a subset of sporadic and familial CH and control participants. Results: The analysis of candidate genes revealed that only allele and genotype frequency of the 2 ADH4 mutations resulted significantly between sporadic CH and controls; the same mutations were homozygous in CH patients from 2 families. The comparative genomic hybridization analysis revealed 2 novel rearrangements that involved the intron regions of thyrotropin-releasing hormone-degrading enzyme and neurexin 3 ( NRXN3 ) genes, respectively. The first arrangement was present either in CH or in controls, whereas the second one 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 NRXN3 gene might be related to CH in a subset of cases. Abstract : Supplemental Digital Content is available in the text.