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Recessive mutation in tetraspanin CD151 causes Kindler syndrome-like epidermolysis bullosa with multi-systemic manifestations including nephropathy
Journal article   Open access   Peer reviewed

Recessive mutation in tetraspanin CD151 causes Kindler syndrome-like epidermolysis bullosa with multi-systemic manifestations including nephropathy

Hassan Vahidnezhad, Leila Youssefian, Amir Hossein Saeidian, Hamidreza Mahmoudi, Andrew Touati, Maryam Abiri, Abdol-Mohammad Kajbafzadeh, Sophia Aristodemou, Lu Liu, John A. McGrath, …
Matrix biology, v 66, pp 22-33
Mar 2018
DOI: https://doi.org/10.1016/j.matbio.2017.11.003
PMID: 29138120
Featured in Collection :   UN Sustainable Development Goals @ Drexel
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https://doi.org/10.1016/j.matbio.2017.11.003View
Published, Version of Record (VoR)Open Access (License Unspecified),  Open

Abstract

CD151 Epidermolysis bullosa Kindler syndrome Nephropathy Next generation sequencing RNA-seq Tetraspanin CD151
Epidermolysis bullosa (EB) is caused by mutations in as many as 19 distinct genes. We have developed a next-generation sequencing (NGS) panel targeting genes known to be mutated in skin fragility disorders, including tetraspanin CD151 expressed in keratinocytes at the dermal-epidermal junction. The NGS panel was applied to a cohort of 92 consanguineous families of unknown subtype of EB. In one family, a homozygous donor splice site mutation in CD151 (NM_139029; c.351+2T>C) at the exon 5/intron 5 border was identified, and RT-PCR and whole transcriptome analysis by RNA-seq confirmed deletion of the entire exon 5 encoding 25 amino acids. Immunofluorescence of proband's skin and Western blot of skin proteins with a monoclonal antibody revealed complete absence of CD151. Transmission electron microscopy showed intracellular disruption and cell-cell dysadhesion of keratinocytes in the lower epidermis. Clinical examination of the 33-year old proband, initially diagnosed as Kindler syndrome, revealed widespread blistering, particularly on pretibial areas, poikiloderma, nail dystrophy, loss of teeth, early onset alopecia, and esophageal webbing and strictures. The patient also had history of nephropathy with proteinuria. Collectively, the results suggest that biallelic loss-of-function mutations in CD151 underlie an autosomal recessive mechano-bullous disease with systemic features. Thus, CD151 should be considered as the 20th causative, EB-associated gene. •Epidermolysis bullosa (EB) is a heterogeneous group of skin fragility disorders•Nineteen genes harbor mutations in different subtypes of EB•A novel mutation in the CD151 gene encoding a tetraspanin molecule was identified by NGS using a targeted 21-gene panel•The pathogenicity of the mutation was confirmed at protein and by RNA-seq.•These studies provide justification for inclusion of CD151 officially as the 20th gene in the classification of EB

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Biochemistry & Molecular Biology
Cell Biology
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