Severe epidermolysis bullosa simplex phenotype caused by codominant mutations p.Ile377Thr in keratin 14 and p.Gly138Glu in keratin 5.


Journal

Experimental dermatology
ISSN: 1600-0625
Titre abrégé: Exp Dermatol
Pays: Denmark
ID NLM: 9301549

Informations de publication

Date de publication:
10 2020
Historique:
received: 23 03 2020
revised: 28 07 2020
accepted: 24 08 2020
pubmed: 5 9 2020
medline: 26 10 2021
entrez: 5 9 2020
Statut: ppublish

Résumé

Epidermolysis bullosa simplex (EBS) is a rare skin disease usually inherited in an autosomal dominant pattern. EBS is resulting from mutations in keratin 5 (KRT5) and keratin 14 (KRT14) genes encoding the keratins 5 and 14 proteins expressed in the keratinocytes of the basal layer of the epidermis. To date, seven pathogenic mutations have been reported to be responsible for EBS in the Canadian population from the province of Quebec: p.Pro25Leu, p.Leu150Pro, p.Met327Thr and p.Arg559X in KRT5; p.Arg125Ser, p.Ile377Thr and p.Ile412Phe in KRT14. Here, we present a novel French-Canadian patient diagnosed with EBS confined to the soles but presenting a severe complication form including blisters, hyperkeratosis, skin erosions and toenail abnormalities. Mutation screening was performed by direct sequencing of the entire coding regions of KRT5 and KRT14 genes and revealed the previously reported missense heterozygous mutation c. 1130T > C in KRT14 (p.Ile377Thr). Furthermore, this patient is carrying a second mutation in KRT5, c.413G > A (p.Gly138Glu), which has been linked to an increased risk of basal cell carcinoma in the literature. We suspect an impact of the p.Gly138Glu variant on the EBS phenotype severity of the studied patient. The pathogenicity and consequences of both genetic variations were simulated by in silico tools.

Identifiants

pubmed: 32885477
doi: 10.1111/exd.14189
doi:

Substances chimiques

KRT14 protein, human 0
KRT15 protein, human 0
Keratin-14 0
Keratin-15 0

Types de publication

Case Reports Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

961-969

Subventions

Organisme : Fondation du grand défi Pierre Lavoie
Organisme : The Rare Disease Foundation
Organisme : DEBRA Canada
Organisme : EB Research Partnership (EBRP)

Informations de copyright

© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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Auteurs

Mbarka Bchetnia (M)

Centre intersectoriel en santé durable, Département des sciences fondamentales, Université du Québec à Chicoutimi (UQAC), Saguenay, QC, Canada.

Jean-Pascal Allard (JP)

Centre intégré universitaire de santé et de services sociaux du Saguenay-Lac-Saint-Jean, Saguenay, QC, Canada.

Anne-Marie Boucher-Lafleur (AM)

Centre intersectoriel en santé durable, Département des sciences fondamentales, Université du Québec à Chicoutimi (UQAC), Saguenay, QC, Canada.

Tania Cruz Marino (T)

Centre intégré universitaire de santé et de services sociaux du Saguenay-Lac-Saint-Jean, Saguenay, QC, Canada.

Audrey Dupéré (A)

Centre intégré universitaire de santé et de services sociaux du Saguenay-Lac-Saint-Jean, Saguenay, QC, Canada.

Julie Powell (J)

Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal, Montréal, QC, Canada.

Catherine McCuaig (C)

Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal, Montréal, QC, Canada.

Marie-Ève Bernier (MÈ)

Centre intégré universitaire de santé et de services sociaux du Saguenay-Lac-Saint-Jean, Saguenay, QC, Canada.

Catherine Laprise (C)

Centre intersectoriel en santé durable, Département des sciences fondamentales, Université du Québec à Chicoutimi (UQAC), Saguenay, QC, Canada.
Centre intégré universitaire de santé et de services sociaux du Saguenay-Lac-Saint-Jean, Saguenay, QC, Canada.

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