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

Dawn H. Siegel, Gabrielle H S Ashton, Homero G. Penagos, James V. Lee, Heidi 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 & 22 others 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

Research output: Contribution to journalArticle

225 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)174-187
Number of pages14
JournalAmerican Journal of Human Genetics
Volume73
Issue number1
DOIs
StatePublished - Jul 1 2003
Externally publishedYes

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Extracellular Matrix Proteins
Caenorhabditis elegans
Extracellular Matrix
Actins
Caenorhabditis elegans Proteins
Skin Pigmentation
Solar System
Keratins
Actin Cytoskeleton
Genes
Atrophy
Skin
Mutation
Membranes
Poikiloderma of Kindler
Proteins

ASJC Scopus subject areas

  • Genetics

Cite this

Loss of kindlin-1, a human homolog of the Caenorhabditis elegans actin-extracellular-matrix linker protein UNC-112, causes Kindler syndrome. / Siegel, Dawn H.; Ashton, Gabrielle H S; Penagos, Homero G.; Lee, James V.; Feiler, Heidi; Wilhelmsen, Kirk C.; South, Andrew P.; Smith, Frances J D; Prescott, Alan R.; Wessagowit, Vesarat; Oyama, Noritaka; Akiyama, Masashi; Al Aboud, Daifullah; Al Aboud, Khalid; Al Githami, Ahmad; Al Hawsawi, Khalid; Al Ismaily, Abla; Al-Suwaid, Raouf; Atherton, David J.; Caputo, Ruggero; Fine, Jo David; Frieden, Ilona J.; Fuchs, Elaine; Haber, Richard M.; Harada, Takashi; Kitajima, Yasuo; Mallory, Susan B.; Ogawa, Hideoki; Sahin, Sedef; Shimizu, Hiroshi; Suga, Yasushi; Tadini, Gianluca; Tsuchiya, Kikuo; Wiebe, Colin B.; Wojnarowska, Fenella; Zaghloul, Adel B.; Hamada, Takahiro; Mallipeddi, Rajeev; Eady, Robin A J; McLean, W. H Irwin; McGrath, John A.; Epstein, Ervin H.

In: American Journal of Human Genetics, Vol. 73, No. 1, 01.07.2003, p. 174-187.

Research output: Contribution to journalArticle

Siegel, DH, Ashton, GHS, Penagos, HG, Lee, JV, Feiler, H, Wilhelmsen, KC, South, AP, Smith, FJD, Prescott, AR, Wessagowit, V, Oyama, N, Akiyama, M, Al Aboud, D, Al Aboud, K, Al Githami, A, Al Hawsawi, K, Al Ismaily, A, Al-Suwaid, R, Atherton, DJ, Caputo, R, Fine, JD, Frieden, IJ, Fuchs, E, Haber, RM, Harada, T, Kitajima, Y, Mallory, SB, Ogawa, H, Sahin, S, Shimizu, H, Suga, Y, Tadini, G, Tsuchiya, K, Wiebe, CB, Wojnarowska, F, Zaghloul, AB, Hamada, T, Mallipeddi, R, Eady, RAJ, McLean, WHI, McGrath, JA & Epstein, EH 2003, 'Loss of kindlin-1, a human homolog of the Caenorhabditis elegans actin-extracellular-matrix linker protein UNC-112, causes Kindler syndrome', American Journal of Human Genetics, vol. 73, no. 1, pp. 174-187. https://doi.org/10.1086/376609
Siegel, Dawn H. ; Ashton, Gabrielle H S ; Penagos, Homero G. ; Lee, James V. ; Feiler, Heidi ; Wilhelmsen, Kirk C. ; South, Andrew P. ; Smith, Frances J D ; Prescott, Alan R. ; Wessagowit, Vesarat ; Oyama, Noritaka ; Akiyama, Masashi ; Al Aboud, Daifullah ; Al Aboud, Khalid ; Al Githami, Ahmad ; Al Hawsawi, Khalid ; Al Ismaily, Abla ; Al-Suwaid, Raouf ; Atherton, David J. ; Caputo, Ruggero ; Fine, Jo David ; Frieden, Ilona J. ; Fuchs, Elaine ; Haber, Richard M. ; Harada, Takashi ; Kitajima, Yasuo ; Mallory, Susan B. ; Ogawa, Hideoki ; Sahin, Sedef ; Shimizu, Hiroshi ; Suga, Yasushi ; Tadini, Gianluca ; Tsuchiya, Kikuo ; Wiebe, Colin B. ; Wojnarowska, Fenella ; Zaghloul, Adel B. ; Hamada, Takahiro ; Mallipeddi, Rajeev ; Eady, Robin A J ; McLean, W. H Irwin ; McGrath, John A. ; Epstein, Ervin H. / Loss of kindlin-1, a human homolog of the Caenorhabditis elegans actin-extracellular-matrix linker protein UNC-112, causes Kindler syndrome. In: American Journal of Human Genetics. 2003 ; Vol. 73, No. 1. pp. 174-187.
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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.",
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T1 - Loss of kindlin-1, a human homolog of the Caenorhabditis elegans actin-extracellular-matrix linker protein UNC-112, causes Kindler syndrome

AU - Siegel, Dawn H.

AU - Ashton, Gabrielle H S

AU - Penagos, Homero G.

AU - Lee, James V.

AU - Feiler, Heidi

AU - Wilhelmsen, Kirk C.

AU - South, Andrew P.

AU - Smith, Frances J D

AU - Prescott, Alan R.

AU - Wessagowit, Vesarat

AU - Oyama, Noritaka

AU - Akiyama, Masashi

AU - Al Aboud, Daifullah

AU - Al Aboud, Khalid

AU - Al Githami, Ahmad

AU - Al Hawsawi, Khalid

AU - Al Ismaily, Abla

AU - Al-Suwaid, Raouf

AU - Atherton, David J.

AU - Caputo, Ruggero

AU - Fine, Jo David

AU - Frieden, Ilona J.

AU - Fuchs, Elaine

AU - Haber, Richard M.

AU - Harada, Takashi

AU - Kitajima, Yasuo

AU - Mallory, Susan B.

AU - Ogawa, Hideoki

AU - Sahin, Sedef

AU - Shimizu, Hiroshi

AU - Suga, Yasushi

AU - Tadini, Gianluca

AU - Tsuchiya, Kikuo

AU - Wiebe, Colin B.

AU - Wojnarowska, Fenella

AU - Zaghloul, Adel B.

AU - Hamada, Takahiro

AU - Mallipeddi, Rajeev

AU - Eady, Robin A J

AU - McLean, W. H Irwin

AU - McGrath, John A.

AU - Epstein, Ervin H.

PY - 2003/7/1

Y1 - 2003/7/1

N2 - 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.

AB - 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.

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JF - American Journal of Human Genetics

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