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

Siegel D., Ashton G., Penagos H., Lee J., Feiler H., Wilhelmsen K., ...Daha Fazla

AMERICAN JOURNAL OF HUMAN GENETICS, cilt.73, sa.1, ss.174-187, 2003 (SCI-Expanded) identifier identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 73 Sayı: 1
  • Basım Tarihi: 2003
  • Doi Numarası: 10.1086/376609
  • Dergi Adı: AMERICAN JOURNAL OF HUMAN GENETICS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.174-187
  • Acıbadem Mehmet Ali Aydınlar Üniversitesi Adresli: Hayır

Özet

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 20p12.3. Loss-of-function mutations were identified in the FLJ20116 gene ( renamed "KIND1" [ 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.