COL6A5 variants in familial neuropathic chronic itch

Filippo Martinelli-Boneschi, Marina Colombi, Marco Castori, Grazia Devigili, Roberto Eleopra, Rayaz A. Malik, Marco Ritelli, Nicoletta Zoppi, Chiara Dordoni, Melissa Sorosina, Paola Grammatico, Hassan Fadavi, Monique M. Gerrits, Rowida Almomani, Catharina G. Faber, Ingemar S. J. Merkies, Daniela Toniolo, Massimiliano Cocca, Claudio Doglioni, Stephen G. WaxmanSulayman D. Dib-Hajj, Michela M. Taiana, Jenny Sassone, Raffaella Lombardi, Daniele Cazzato, Andrea Zauli, Silvia Santoro, Margherita Marchi, Giuseppe Lauria*, INGI Network

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Itch is thought to represent the peculiar response to stimuli conveyed by somatosensory pathways shared with pain through the activation of specific neurons and receptors. It can occur in association with dermatological, systemic and neurological diseases, or be the side effect of certain drugs. However, some patients suffer from chronic idiopathic itch that is frequently ascribed to psychological distress and for which no biomarker is available to date. We investigated three multigenerational families, one of which diagnosed with joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type (JHS/EDS-HT), characterized by idiopathic chronic itch with predominantly proximal distribution. Skin biopsy was performed in all eight affected members and revealed in six of them reduced intraepidermal nerve fibre density consistent with small fibre neuropathy. Whole exome sequencing identified two COL6A5 rare variants co-segregating with chronic itch in eight affected members and absent in non-affected members, and in one unrelated sporadic patient with type 1 painless diabetic neuropathy and chronic itch. Two families and the diabetic patient carried the nonsense c.6814G>T (p.Glu2272*) variant and another family carried the missense c.6486G>C (p.Arg2162Ser) variant. Both variants were predicted as likely pathogenic by in silico analyses. The two variants were rare (minor allele frequency

Original languageEnglish
Pages (from-to)555-567
Number of pages13
JournalBrain
Volume140
DOIs
Publication statusPublished - Mar 2017

Keywords

  • itch
  • COL6A5
  • small fibre neuropathy
  • neuropathic pain
  • SMALL FIBER NEUROPATHY
  • SENSORY NEURONS
  • CHRONIC PRURITUS
  • ATOPIC-DERMATITIS
  • SODIUM-CHANNELS
  • PAIN
  • NOCICEPTORS
  • GABAPENTIN
  • SYMPTOMS
  • CHAINS

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