Forschung & Innovation
Publikationen
A Novel Homozygous 9385 bp Deletion in the FERMT1 (KIND1) Gene in a Malaysian Family with Kindler Epidermolysis bullosa and a Review of Large Deletions
PMU Autor*innen
Alfred Klausegger, Martin Laimer, Johann Wolfgang Bauer
Alle Autor*innen
Alfred Klausegger, Fabian Leditzky, Susanne Krämer, Francis Palisson, María Joao Yubero, Sebastián Véliz, Mark Jean Aan Koh, Ene-Choo Tan, Martin Laimer, Johann Wolfgang Bauer, Ignacia Fuentes
Fachzeitschrift
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Kurzfassung
Kindler Epidermolysis bullosa (KEB; OMIM 173650) is a rare autosomal recessive genodermatosis characterized by bullous poikiloderma and photosensitivity. Additional presentations include blistering, poor wound healing, skin atrophy, and increased risk of skin cancer. Most cases of KEB result from aberrations in the FERMT1 (Fermitin family member 1) gene encoding kindlin-1 and include nonsense, frameshift, splicing, and missense variants. Large deletion variants have been reported in nine cases to date. Most variants are predicted to lead to premature termination of translation and to loss of kindlin-1 function. In this study, we report on a 33-year-old male patient who presented with typical clinical manifestations of KEB. As routine molecular testing failed to obtain a diagnosis, Next Generation Sequencing (NGS) of an Epidermolysis Bullosa (EB)-specific panel was carried out followed by the determination of the deletion breakpoints and verification at the mRNA and protein levels. This approach revealed a new large homozygous deletion of ~9.4 kb in the FERMT1 gene involving exons 7 to 9. Finally, we performed a literature review on large FERMT1 deletions. The deletion is predicted to skip exons 7 to 9 within the mRNA, which results in a frameshift. The patient's phenotype is likely caused by the resulting truncated and non-functioning protein. Our report further enriches the spectrum of FERMT1 gene variants to improve genotype-phenotype correlations.
Keywords
Humans, Male, DELETION, ADULT, Membrane Proteins/genetics, Epidermolysis Bullosa/genetics, Homozygote, Neoplasm Proteins/genetics, Sequence Deletion, Photosensitivity Disorders/genetics, Pedigree, Periodontal Diseases/genetics, Malaysia, Blister/genetics, Exons, Fermt1, Kindler Epidermolysis bullosa, Poikiloderma, Amelogenesis imperfecta