Laminin-5 mutational analysis in an Italian cohort of patients with junctional epidermolysis bullosa

The Journal of Investigative Dermatology
Patrizia PosteraroD Castiglia

Abstract

Junctional epidermolysis bullosa (JEB) is a rare genodermatosis characterized by dermal-epidermal separation that is caused by mutations in the genes encoding hemidesmosomal components and laminin-5, the major epithelial adhesion ligand. Here, we report on the mutational analysis of LAMA3, LAMB3, and LAMC2 genes encoding laminin-5 chains in 19 Italian patients, 11 affected with the severe Herlitz (H JEB) and eight with the mild non-Herlitz variant of JEB (non-H JEB). Eighteen mutations, seven of which were novel, were identified and their consequences analyzed at the mRNA and protein level. Premature termination codon mutations in both alleles of LAMB3 or LAMC2 genes were found in nine of the 11 H JEB patients, with a prevalence of mutations in LAMC2. In one case, a homozygous frameshift mutation in LAMB3 was associated to illegitimate splicing leading to non-H JEB. One H JEB patient showed a large intragenic duplication within LAMC2, a genetic defect so far uncovered in laminin-5 genes. Splicing or missense mutations, were prevalent in non-H JEB patients. Collectively, five mutations appeared to be frequent in laminin-5 JEB patients: R635X, 29insC, E210K, W143X in LAMB3 and R95X in LAMC2. These recurrent mutations account for ...Continue Reading

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Citations

Dec 1, 2009·Dermatologic Clinics·Daniele Castiglia, Giovanna Zambruno
Sep 18, 2004·The Journal of Investigative Dermatology·Jouni Uitto
May 8, 2010·Dermatologic Clinics·Daniele Castiglia, Giovanna Zambruno
Dec 15, 2005·Advances in Dermatology·Josephine Chu McAllister, M Peter Marinkovich
May 16, 2019·The British Journal of Dermatology·C HasG Zambruno
Mar 18, 2020·Expert Opinion on Biological Therapy·Allison R KeithJakub Tolar
Mar 4, 2020·Journal of the European Academy of Dermatology and Venereology : JEADV·R MittwollenJ Hammersen
Feb 20, 2020·Italian Journal of Pediatrics·Ingrid Anne Mandy SchierzEttore Piro
Feb 26, 2020·International Journal of Molecular Sciences·Paola FortugnoDaniele Castiglia
Sep 26, 2020·Nature Reviews. Disease Primers·Ajoy BardhanAdrian H Heagerty
Aug 31, 2021·Frontiers in Genetics·Liam ShawKevin J Hamill

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