Kindler syndrome: a focal adhesion genodermatosis.
Kindler syndrome (OMIM 173650) is an autosomal recessive genodermatosis characterized by trauma-induced blistering, poikiloderma, skin atrophy, mucosal inflammation and varying degrees of photosensitivity. Although Kindler syndrome is classified as a subtype of epidermolysis bullosa, it has distinct clinicopathological and molecular abnormalities. The molecular pathology of Kindler syndrome involves loss-of-function mutations in a newly recognized actin cytoskeleton-associated protein, now known as fermitin family homologue 1, encoded by the gene FERMT1. This protein mediates anchorage between the actin cytoskeleton and the extracellular matrix via focal adhesions, and thus the structural pathology differs from other forms of epidermolysis bullosa in which there is a disruption of the keratin intermediate filament-hemidesmosome network and the extracellular matrix. In the skin, fermitin family homologue 1 is mainly expressed in basal keratinocytes and binds to the cytoplasmic tails of beta1 and beta3 integrins as well as to fermitin family homologue 2 and filamin-binding LIM protein 1. It also plays a crucial role in keratinocyte migration, proliferation and adhesion. In this report, we review the clinical, cellular and molecular pathology of Kindler syndrome and discuss the role of fermitin family homologue 1 in keratinocyte biology.
Lai-Cheong
J E
JE
Genetic Skin Disease Group, St John's Institute of Dermatology, King's College London, Guy's Campus, London SE1 9RT, UK.
Tanaka
A
A
Hawche
G
G
Emanuel
P
P
Maari
C
C
Taskesen
M
M
Akdeniz
S
S
Liu
L
L
McGrath
J A
JA
D001768:Blister / Q000235:genetics / Q000473:pathology; D004820:Epidermolysis Bullosa / Q000235:genetics* / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D022001:Focal Adhesions / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D010510:Periodontal Diseases / Q000235:genetics*; D010787:Photosensitivity Disorders / Q000235:genetics*; D013577:Syndrome
D016326:Extracellular Matrix Proteins; C475301:FERMT1 protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins