title: 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.affiliation: Department of Dermatology, San Francisco General Hospital, University of California-San Francisco, 1001 Potrero Avenue, San Francisco, CA 94110, USA.
authors.forename: Dawn H
authors.initials: DH
authors.lastname: Siegel
authors.forename: Gabrielle H S
authors.initials: GH
authors.lastname: Ashton
authors.forename: Homero G
authors.initials: HG
authors.lastname: Penagos
authors.forename: James V
authors.initials: JV
authors.lastname: Lee
authors.forename: Heidi S
authors.initials: HS
authors.lastname: Feiler
authors.forename: Kirk C
authors.initials: KC
authors.lastname: Wilhelmsen
authors.forename: Andrew P
authors.initials: AP
authors.lastname: South
authors.forename: Frances J D
authors.initials: FJ
authors.lastname: Smith
authors.forename: Alan R
authors.initials: AR
authors.lastname: Prescott
authors.forename: Vesarat
authors.initials: V
authors.lastname: Wessagowit
authors.forename: Noritaka
authors.initials: N
authors.lastname: Oyama
authors.forename: Masashi
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authors.lastname: Akiyama
authors.forename: Daifullah
authors.initials: D
authors.lastname: Al Aboud
authors.forename: Khalid
authors.initials: K
authors.lastname: Al Aboud
authors.forename: Ahmad
authors.initials: A
authors.lastname: Al Githami
authors.forename: Khalid
authors.initials: K
authors.lastname: Al Hawsawi
authors.forename: Abla
authors.initials: A
authors.lastname: Al Ismaily
authors.forename: Raouf
authors.initials: R
authors.lastname: Al-Suwaid
authors.forename: David J
authors.initials: DJ
authors.lastname: Atherton
authors.forename: Ruggero
authors.initials: R
authors.lastname: Caputo
authors.forename: Jo-David
authors.initials: JD
authors.lastname: Fine
authors.forename: Ilona J
authors.initials: IJ
authors.lastname: Frieden
authors.forename: Elaine
authors.initials: E
authors.lastname: Fuchs
authors.forename: Richard M
authors.initials: RM
authors.lastname: Haber
authors.forename: Takashi
authors.initials: T
authors.lastname: Harada
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Kitajima
authors.forename: Susan B
authors.initials: SB
authors.lastname: Mallory
authors.forename: Hideoki
authors.initials: H
authors.lastname: Ogawa
authors.forename: Sedef
authors.initials: S
authors.lastname: Sahin
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shimizu
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Suga
authors.forename: Gianluca
authors.initials: G
authors.lastname: Tadini
authors.forename: Kikuo
authors.initials: K
authors.lastname: Tsuchiya
authors.forename: Colin B
authors.initials: CB
authors.lastname: Wiebe
authors.forename: Fenella
authors.initials: F
authors.lastname: Wojnarowska
authors.forename: Adel B
authors.initials: AB
authors.lastname: Zaghloul
authors.forename: Takahiro
authors.initials: T
authors.lastname: Hamada
authors.forename: Rajeev
authors.initials: R
authors.lastname: Mallipeddi
authors.forename: Robin A J
authors.initials: RA
authors.lastname: Eady
authors.forename: W H Irwin
authors.initials: WH
authors.lastname: McLean
authors.forename: John A
authors.initials: JA
authors.lastname: McGrath
authors.forename: Ervin H
authors.initials: EH
authors.lastname: Epstein
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D017173:Caenorhabditis elegans / Q000235:genetics*; D002890:Chromosomes, Human, Pair 20; D017931:DNA Primers; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D010375:Pedigree; D017386:Sequence Homology, Amino Acid; D013577:Syndrome
chemical_list: D017931:DNA Primers; D016326:Extracellular Matrix Proteins; C475301:FERMT1 protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins