TY - JOUR
T1 - C-terminally truncated kindlin-1 leads to abnormal adhesion and migration of keratinocytes
AU - Has, C.
AU - Ludwig, R. J.
AU - Herz, C.
AU - Kern, J. S.
AU - Ussar, S.
AU - Ochsendorf, F. R.
AU - Kaufmann, R.
AU - Schumann, H.
AU - Kohlhase, J.
AU - Bruckner-Tuderman, L.
PY - 2008/11/1
Y1 - 2008/11/1
N2 - 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. Objectives: 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. Conclusion: A C-terminally truncated kindlin-1 in keratinocytes could not function correctly even if it were expressed.
AB - 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. Objectives: 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. Conclusion: A C-terminally truncated kindlin-1 in keratinocytes could not function correctly even if it were expressed.
UR - http://www.scopus.com/inward/record.url?scp=54249105508&partnerID=8YFLogxK
U2 - 10.1111/j.1365-2133.2008.08760.x
DO - 10.1111/j.1365-2133.2008.08760.x
M3 - Journal articles
C2 - 18652585
AN - SCOPUS:54249105508
SN - 0007-0963
VL - 159
SP - 1192
EP - 1196
JO - British Journal of Dermatology
JF - British Journal of Dermatology
IS - 5
ER -