Loss of kindlin-1, a human homolog of the Caenorhabditis elegans actin-extracellular-matrix linker protein UNC-112, causes Kindler syndrome.

[kindler syndrome]

Kindler syndrome is an autosomal recessive disorder characterized by neonatal blistering , sun sensitivity , atrophy , abnormal pigmentation , and fragility of the skin . Linkage and homozygosity analysis in an isolated Panamanian cohort and in additional inbred families mapped the gene to 20 p 12 .3 . Loss -of-function mutations were identified in the FLJ 20116 gene (renamed "KIND 1 " [encoding kindlin-1 ]). Kindlin-1 is a human homolog of the Caenorhabditis elegans protein UNC-112 , a membrane-associated structural /signaling protein that has been implicated in linking the actin cytoskeleton to the extracellular matrix (ECM ). Thus , Kindler syndrome is , to our knowledge , the first skin fragility disorder caused by a defect in actin-ECM linkage , rather than keratin-ECM linkage .

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