C-terminally truncated kindlin-1 leads to abnormal adhesion and migration of keratinocytes.
BACKGROUND
The Kindler syndrome (KS) protein kindlin-1 is a member of a protein complex that links cortical actin to integrins on the surface of basal keratinocytes. Loss of kindlin-1 leads to abnormalities of cell adhesion and motility, and to skin blistering and progressive poikiloderma as clinical symptoms.


OBJECTIVE
Here we investigated a severely affected patient, disclosed the mutation that caused the disease and delineated its biological consequences.


METHODS
Mutation screening of the kindlin-1 gene, KIND1 (now called FERMT1), was performed with polymerase chain reaction (PCR) amplification of all exons and sequencing. Mutated kindlin-1 was characterized by reverse transcriptase (RT)-PCR and immunoblotting, and genotype-phenotype correlations were analysed using immunohistochemical staining of skin biopsies and keratinocytes from the patient's skin. Cell adhesion and motility were assessed with functional tests.


RESULTS
We disclosed a splice site mutation in the first position of intron 13 of the FERMT1 gene, which caused skipping of exon 13. The short transcript partially escaped nonsense-mediated mRNA decay and was translated into a truncated protein.


CONCLUSIONS
A C-terminally truncated kindlin-1 in keratinocytes could not function correctly even if it were expressed.
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Department of Dermatology, University Medical Center Freiburg, Hauptstr. 7, 79104 Freiburg, Germany.
Ludwig
R J
RJ
Herz
C
C
Kern
J S
JS
Ussar
S
S
Ochsendorf
F R
FR
Kaufmann
R
R
Schumann
H
H
Kohlhase
J
J
Bruckner-Tuderman
L
L
D000328:Adult; D002448:Cell Adhesion / Q000235:genetics*; D005091:Exons; D016368:Frameshift Mutation; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000166:cytology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012873:Skin Diseases, Genetic / Q000235:genetics / Q000473:pathology*
C475301:FERMT1 protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins