Kindler syndrome in mice and men.

[kindler syndrome]

Kindler syndrome (KS ) in humans is a severe skin blistering disease associated with inflammation and increased risk of epidermal squamous cell carcinoma (SCC ). This disease is known to be caused by loss -of-function mutations in Kindlin-1 , a focal adhesion β-integrin binding protein . Thus far , it has been unclear what specific signaling events occur in KS keratinocytes to promote tumorigenesis , especially since loss of β-integrins and focal adhesion complexes has been previously shown to prevent or delay tumor formation . In the April issue of Nature Medicine , Rognoni and colleagues generate a transgenic mouse lacking Kindlin-1 in the epidermis to model the key features of KS , and show that Kindlin-1 regulates Wnt and TGF β signaling independent of β-integrins . These β 1 -integrin-independent functions of Kindlin-1 may contribute to the increased SCC risk in KS patients .

Diseases
Validation

Diseases presenting "loss-of-function mutations" symptom

achondroplasia

alpha-thalassemia

aromatase deficiency

child syndrome

cowden syndrome

dystrophic epidermolysis bullosa

epidermolysis bullosa simplex

erythropoietic protoporphyria

esophageal adenocarcinoma

familial hypocalciuric hypercalcemia

harlequin ichthyosis

hirschsprung disease

kallmann syndrome

kindler syndrome

lamellar ichthyosis

neonatal adrenoleukodystrophy

pendred syndrome

werner syndrome

x-linked adrenoleukodystrophy

This symptom has already been validated