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.
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.
Authors: Joey E Lai-Cheong; Maddy Parsons; Akio Tanaka; Siegfried Ussar; Andrew P South; Sethuraman Gomathy; John B Mee; Jean-Baptiste Barbaroux; Tanasit Techanukul; Noor Almaani; Suzanne E Clements; Ian R Hart; John A McGrath Journal: Am J Pathol Date: 2009-09-17 Impact factor: 4.307
Authors: Elisabeth Zapatero-Solana; Jose Luis García-Giménez; Sara Guerrero-Aspizua; Marta García; Agustí Toll; Eulalia Baselga; Maria Durán-Moreno; Jelena Markovic; Jose Manuel García-Verdugo; Claudio J Conti; Cristina Has; Fernando Larcher; Federico V Pallardó; Marcela Del Rio Journal: Orphanet J Rare Dis Date: 2014-12-21 Impact factor: 4.123
Authors: Magdalene Michael; Rumena Begum; Grace K Chan; Austin J Whitewood; Daniel R Matthews; Benjamin T Goult; John A McGrath; Maddy Parsons Journal: J Invest Dermatol Date: 2018-09-21 Impact factor: 8.551