Loss of kindlin-1, a human homolog of the Caenorhabditis elegans actin-extracellular-matrix linker protein UNC-112, causes 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 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.
Siegel
Dawn H
DH
Department of Dermatology, San Francisco General Hospital, University of California-San Francisco, 1001 Potrero Avenue, San Francisco, CA 94110, USA.
Ashton
Gabrielle H S
GH
Penagos
Homero G
HG
Lee
James V
JV
Feiler
Heidi S
HS
Wilhelmsen
Kirk C
KC
South
Andrew P
AP
Smith
Frances J D
FJ
Prescott
Alan R
AR
Wessagowit
Vesarat
V
Oyama
Noritaka
N
Akiyama
Masashi
M
Al Aboud
Daifullah
D
Al Aboud
Khalid
K
Al Githami
Ahmad
A
Al Hawsawi
Khalid
K
Al Ismaily
Abla
A
Al-Suwaid
Raouf
R
Atherton
David J
DJ
Caputo
Ruggero
R
Fine
Jo-David
JD
Frieden
Ilona J
IJ
Fuchs
Elaine
E
Haber
Richard M
RM
Harada
Takashi
T
Kitajima
Yasuo
Y
Mallory
Susan B
SB
Ogawa
Hideoki
H
Sahin
Sedef
S
Shimizu
Hiroshi
H
Suga
Yasushi
Y
Tadini
Gianluca
G
Tsuchiya
Kikuo
K
Wiebe
Colin B
CB
Wojnarowska
Fenella
F
Zaghloul
Adel B
AB
Hamada
Takahiro
T
Mallipeddi
Rajeev
R
Eady
Robin A J
RA
McLean
W H Irwin
WH
McGrath
John A
JA
Epstein
Ervin H
EH
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
D017931:DNA Primers; D016326:Extracellular Matrix Proteins; C475301:FERMT1 protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins