Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 555-567 |
| Number of pages | 13 |
| Journal | Brain |
| Volume | 140 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 2017 |
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COL6A5 variants in familial neuropathic chronic itch. / Martinelli-Boneschi, F; Colombi, M; Castori, M; Devigili, G; Eleopra, R; Malik, RA; Ritelli, M; Zoppi, N; Dordoni, C; Sorosina, M; Grammatico, P; Fadavi, H; Gerrits, MM; Almomani, R; Faber, CG; Merkies, ISJ; Toniolo, D; Cocca, Massimiliano; Doglioni, C; Waxman, SG; Dib-Hajj, SD; Taiana, MM; Sassone, J; Lombardi, R; Cazzato, D; Zauli, A; Santoro, S; Marchi, M; Lauria, G.
In: Brain, Vol. 140, No. 3, 2017, p. 555-567.Research output: Contribution to journal › Article
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TY - JOUR
T1 - COL6A5 variants in familial neuropathic chronic itch
AU - Martinelli-Boneschi, F
AU - Colombi, M
AU - Castori, M
AU - Devigili, G
AU - Eleopra, R
AU - Malik, RA
AU - Ritelli, M
AU - Zoppi, N
AU - Dordoni, C
AU - Sorosina, M
AU - Grammatico, P
AU - Fadavi, H
AU - Gerrits, MM
AU - Almomani, R
AU - Faber, CG
AU - Merkies, ISJ
AU - Toniolo, D
AU - Cocca, Massimiliano
AU - Doglioni, C
AU - Waxman, SG
AU - Dib-Hajj, SD
AU - Taiana, MM
AU - Sassone, J
AU - Lombardi, R
AU - Cazzato, D
AU - Zauli, A
AU - Santoro, S
AU - Marchi, M
AU - Lauria, G
PY - 2017
Y1 - 2017
N2 - 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.6486G4C (p.Arg2162Ser) variant. Both variants were predicted as likely pathogenic by in silico analyses. The two variants were rare (minor allele frequency
AB - 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.6486G4C (p.Arg2162Ser) variant. Both variants were predicted as likely pathogenic by in silico analyses. The two variants were rare (minor allele frequency
U2 - 10.1093/brain/aww343
DO - 10.1093/brain/aww343
M3 - Article
VL - 140
SP - 555
EP - 567
JO - Brain
JF - Brain
SN - 0006-8950
IS - 3
ER -