Kindler syndrome pathogenesis and fermitin family homologue 1 (kindlin-1) function.
Kindler syndrome is caused by genetic defects in the focal contact-associated protein, fermitin family homologue 1 (FFH1), encoded by the gene FERMT1 (known as KIND1). Defects in FFH1 lead to abnormal integrin activation and loss of keratinocyte epidermal adhesion to the underlying basal lamina, disruption in normal cell cytoskeleton within keratinocytes, and altered signaling pathways, leading to increased extracellular matrix production. Null mutations in FERMT1 result in skin blistering from birth and early childhood progressive poikiloderma, mucosal fragility, and increased risk of cancer. The complete range of FFH1 functions in skin and other epithelia has yet to be determined.
D'Souza
Maria-Anna M A
MA
Children's Centre for Burns Research, The University of Queensland, Queensland Children's Medical Research Institute, L/4 RCH Foundation Building, Herston, Brisbane, Queensland 4029, Australia.
Kimble
Roy M
RM
McMillan
James R
JR
D018450:Disease Progression; D004817:Epidermis / Q000473:pathology; D004820:Epidermolysis Bullosa / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology*; D009363:Neoplasm Proteins / Q000235:genetics* / Q000502:physiology*; D012878:Skin Neoplasms / Q000235:genetics / Q000473:pathology; D013577:Syndrome
C475301:FERMT1 protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins