Biallelic KRT5 mutations in autosomal recessive epidermolysis bullosa simplex, including a complete human keratin 5 “knock-out”

Beitrag in einer Fachzeitschrift


Details zur Publikation

Autorinnen und Autoren: Vahidnezhad H, Youssefian L, Daneshpazhooh M, Mahmoudi H, Kariminejad A, Fischer J, Christiansen J, Schneider H, Guy A, Liu L, McGrath JA, Has C, Uitto J
Zeitschrift: Matrix Biology
Jahr der Veröffentlichung: 2019
ISSN: 0945-053X


Abstract

Epidermolysis bullosa simplex (EBS) is usually inherited as an autosomal dominant disease due to monoallelic gain-of-function mutations in KRT5 or KRT14. Although autosomal recessive forms of EBS have been associated with mutations in at least 10 genes, recessive EBS due to homozygous biallelic KRT5 mutations has not been reported previously; it has been hypothesized that it would result in prenatal lethality. We sought the genetic causes of EB in a cohort of 512 distinct EB families by performing whole exome sequencing (WES) and using an EB-targeting next-generation sequencing (NGS) panel of 21 genes. The pathogenicity and consequences of the mutations were determined by expression profiling and at tissue and ultrastructural levels. Two pathogenic, homozygous missense variants of KRT5 in two patients with generalized EBS and a homozygous null mutation in a patient who died as a neonate from complications of EB were found. The two missense mutations disrupted keratin 5 expression on immunofluorescence microscopy, and the human “knock-out” of KRT5 showed no RNA and protein expression. Collectively, these findings identify biallelic KRT5 mutations with a phenotypic spectrum varying from mild, localized and generalized to perinatal lethal, expanding the genotypic profile of autosomal recessive EBS.


FAU-Autorinnen und Autoren / FAU-Herausgeberinnen und Herausgeber

Schneider, Holm Prof. Dr.
Professur für Kinderheilkunde/Experimentelle Perinatalmedizin


Einrichtungen weiterer Autorinnen und Autoren

Albert-Ludwigs-Universität Freiburg
Guy's and St Thomas'
Kariminejad & Najmabadi Pathology and Genetics Center
King’s College London
Skåne University Hospital / Skånes universitetssjukhus
Tehran University of Medical Sciences
Thomas Jefferson University


Zitierweisen

APA:
Vahidnezhad, H., Youssefian, L., Daneshpazhooh, M., Mahmoudi, H., Kariminejad, A., Fischer, J.,... Uitto, J. (2019). Biallelic KRT5 mutations in autosomal recessive epidermolysis bullosa simplex, including a complete human keratin 5 “knock-out”. Matrix Biology. https://dx.doi.org/10.1016/j.matbio.2019.07.002

MLA:
Vahidnezhad, Hassan, et al. "Biallelic KRT5 mutations in autosomal recessive epidermolysis bullosa simplex, including a complete human keratin 5 “knock-out”." Matrix Biology (2019).

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Zuletzt aktualisiert 2019-07-08 um 22:08