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Molecular analysis of cluster headache.

Federica Zarrilli1, Rossella Tomaiuolo, Carlo Ceglia

  • 1*Dipartimento di Bioscienze e Territorio, Università del Molise, Isernia, Italy †Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli Federico II, Naples, Italy §Dipartimento di Medicina Clinica e Chirurgia, Università di Napoli Federico II, Naples, Italy ∥Dipartimento di Neuroscienze e Scienze Riproduttive e Odontostomatologiche, Università di Napoli Federico II, Naples, Italy ‡CEINGE-Biotecnologie Avanzate, Naples, Italy.

The Clinical Journal of Pain
|January 29, 2014
PubMed
Summary

Genetic analysis of cluster headache (CH) identified alcohol dehydrogenase 4 (ADH4) mutations and a neurexin 3 (NRXN3) gene rearrangement associated with CH in some patients.

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Area of Science:

  • Genetics
  • Neurology

Background:

  • Cluster headache (CH) presents as severe, recurrent unilateral attacks.
  • Previous genetic studies in sporadic CH have yielded conflicting results.

Purpose of the Study:

  • Investigate gene mutations in candidate genes (hypocretin receptor 2, Clock, alcohol dehydrogenase 4 [ADH4]) in sporadic CH.
  • Perform whole-genome scanning using comparative genomic hybridization to identify DNA rearrangements in CH patients.

Main Methods:

  • Analyzed candidate gene mutations in 54 sporadic CH patients and 200 controls.
  • Examined 8 kindreds/families with affected and nonaffected individuals.
  • Conducted whole-genome comparative genomic hybridization on a subset of CH and control participants.

Main Results:

  • Significant differences in allele and genotype frequencies of two ADH4 mutations were found between sporadic CH patients and controls.
  • These ADH4 mutations were homozygous in CH patients from two families.
  • Two novel rearrangements were identified: one in the intron of thyrotropin-releasing hormone-degrading enzyme (present in CH and controls), and another in neurexin 3 (NRXN3) (specific to some CH cases).

Conclusions:

  • The study suggests genetic heterogeneity in CH.
  • Mutations in the ADH4 gene and a novel rearrangement in the NRXN3 gene may be associated with CH in a subset of patients.