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

Abstract

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.

• Authors: Dawn H Siegel, Gabrielle H S Ashton, Homero G Penagos, James V Lee, Heidi S Feiler, Kirk C Wilhelmsen, Andrew P South, Frances J D Smith, Alan R Prescott, Vesarat Wessagowit, Noritaka Oyama, Masashi Akiyama, Daifullah Al Aboud, Khalid Al Aboud, Ahmad Al Githami, Khalid Al Hawsawi, Abla Al Ismaily, Raouf Al-Suwaid, David J Atherton, Ruggero Caputo, Jo-David Fine, Ilona J Frieden, Elaine Fuchs, Richard M Haber, Takashi Harada, Yasuo Kitajima, Susan B Mallory, Hideoki Ogawa, Sedef Sahin, Hiroshi Shimizu, Yasushi Suga, Gianluca Tadini, Kikuo Tsuchiya, Colin B Wiebe, Fenella Wojnarowska, Adel B Zaghloul, Takahiro Hamada, Rajeev Mallipeddi, Robin A J Eady, W H Irwin McLean, John A McGrath, Ervin H Epstein
• Journal: American journal of human genetics (Am J Hum Genet) Vol. 73 Issue 1 Pg. 174-87 (Jul 2003) ISSN: 0002-9297 [Print] United States
• PMID: 12789646 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• DNA Primers
• Extracellular Matrix Proteins
• FERMT1 protein, human
• Membrane Proteins
• Neoplasm Proteins

Topics

• Abnormalities, Multiple (genetics)
• Amino Acid Sequence
• Animals
• Base Sequence
• Blotting, Northern
• Caenorhabditis elegans (genetics)
• Chromosomes, Human, Pair 20
• DNA Primers
• Extracellular Matrix Proteins (genetics)
• Female
• Genetic Linkage
• Humans
• Male
• Membrane Proteins
• Molecular Sequence Data
• Neoplasm Proteins
• Pedigree
• Sequence Homology, Amino Acid
• Syndrome