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

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.

Subjects

adult

;

blister

;

epidermolysis bullosa

;

exons

;

homozygote

;

humans

;

malaysia

;

male

;

membrane proteins

;

neoplasm proteins

;

pedigree

;

periodontal diseases

;

photosensitivity disorders

;

poikiloderma of kindler

;

sequence deletion

;

messenger rna

;

fermt1 protein

;

human

;

membrane protein

;

tumor protein

;

adult

;

article

;

blister

;

cancer risk

;

case report

;

clinical article

;

controlled study

;

epidermolysis bullosa

;

exon

;

familial disease

;

fermt1 gene

;

frameshift mutation

;

gene

;

gene deletion

;

genetic variability

;

genotype phenotype correlation

;

high throughput sequencing

;

homozygosity

;

human

;

human cell

;

human tissue

;

malaysian

;

male

;

photosensitivity

;

poikiloderma

;

skin atrophy

;

skin cancer

;

wound healing impairment

;

blister

;

epidermolysis bullosa

;

genetics

;

homozygote

;

malaysia

;

pathology

;

pedigree

;

periodontal disease

;

photosensitivity disorder

;

amelogenesis imperfecta

;

deletion

;

fermt1

;

kindler epidermolysis bullosa

;

poikiloderma