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A missense mutation in the aggrecan C-type lectin domain disrupts extracellular matrix interactions and causes dominant familial osteochondritis dissecans

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Standard

A missense mutation in the aggrecan C-type lectin domain disrupts extracellular matrix interactions and causes dominant familial osteochondritis dissecans. / Stattin, Eva-Lena; Wiklund, Fredrik; Lindblom, Karin; Onnerfjord, Patrik; Jonsson, Björn-Anders; Tegner, Yelverton; Sasaki, Takako; Struglics, André; Lohmander, Stefan; Dahl, Niklas; Heinegård, Dick; Aspberg, Anders.

I: American Journal of Human Genetics, Bind 86, Nr. 2, 2010, s. 126-37.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Stattin, E-L, Wiklund, F, Lindblom, K, Onnerfjord, P, Jonsson, B-A, Tegner, Y, Sasaki, T, Struglics, A, Lohmander, S, Dahl, N, Heinegård, D & Aspberg, A 2010, 'A missense mutation in the aggrecan C-type lectin domain disrupts extracellular matrix interactions and causes dominant familial osteochondritis dissecans', American Journal of Human Genetics, bind 86, nr. 2, s. 126-37. https://doi.org/10.1016/j.ajhg.2009.12.018

APA

Stattin, E-L., Wiklund, F., Lindblom, K., Onnerfjord, P., Jonsson, B-A., Tegner, Y., ... Aspberg, A. (2010). A missense mutation in the aggrecan C-type lectin domain disrupts extracellular matrix interactions and causes dominant familial osteochondritis dissecans. American Journal of Human Genetics, 86(2), 126-37. https://doi.org/10.1016/j.ajhg.2009.12.018

Vancouver

Stattin E-L, Wiklund F, Lindblom K, Onnerfjord P, Jonsson B-A, Tegner Y o.a. A missense mutation in the aggrecan C-type lectin domain disrupts extracellular matrix interactions and causes dominant familial osteochondritis dissecans. American Journal of Human Genetics. 2010;86(2):126-37. https://doi.org/10.1016/j.ajhg.2009.12.018

Author

Stattin, Eva-Lena ; Wiklund, Fredrik ; Lindblom, Karin ; Onnerfjord, Patrik ; Jonsson, Björn-Anders ; Tegner, Yelverton ; Sasaki, Takako ; Struglics, André ; Lohmander, Stefan ; Dahl, Niklas ; Heinegård, Dick ; Aspberg, Anders. / A missense mutation in the aggrecan C-type lectin domain disrupts extracellular matrix interactions and causes dominant familial osteochondritis dissecans. I: American Journal of Human Genetics. 2010 ; Bind 86, Nr. 2. s. 126-37.

Bibtex

@article{6b7886002b6b11df8ed1000ea68e967b,
title = "A missense mutation in the aggrecan C-type lectin domain disrupts extracellular matrix interactions and causes dominant familial osteochondritis dissecans",
abstract = "Osteochondritis dissecans is a disorder in which fragments of articular cartilage and subchondral bone dislodge from the joint surface. We analyzed a five-generation family in which affected members had autosomal-dominant familial osteochondritis dissecans. A genome-wide linkage analysis identified aggrecan (ACAN) as a prime candidate gene for the disorder. Sequence analysis of ACAN revealed heterozygosity for a missense mutation (c.6907G > A) in affected individuals, resulting in a p.V2303M amino acid substitution in the aggrecan G3 domain C-type lectin, which mediates interactions with other proteins in the cartilage extracellular matrix. Binding studies with recombinant mutated and wild-type G3 proteins showed loss of fibulin-1, fibulin-2, and tenascin-R interactions for the V2303M protein. Mass spectrometric analyses of aggrecan purified from patient cartilage verified that V2303M aggrecan is produced and present in the tissue. Our results provide a molecular mechanism for the etiology of familial osteochondritis dissecans and show the importance of the aggrecan C-type lectin interactions for cartilage function in vivo.",
author = "Eva-Lena Stattin and Fredrik Wiklund and Karin Lindblom and Patrik Onnerfjord and Bj{\"o}rn-Anders Jonsson and Yelverton Tegner and Takako Sasaki and Andr{\'e} Struglics and Stefan Lohmander and Niklas Dahl and Dick Heineg{\aa}rd and Anders Aspberg",
year = "2010",
doi = "10.1016/j.ajhg.2009.12.018",
language = "English",
volume = "86",
pages = "126--37",
journal = "American Journal of Human Genetics",
issn = "0002-9297",
publisher = "Cell Press",
number = "2",

}

RIS

TY - JOUR

T1 - A missense mutation in the aggrecan C-type lectin domain disrupts extracellular matrix interactions and causes dominant familial osteochondritis dissecans

AU - Stattin, Eva-Lena

AU - Wiklund, Fredrik

AU - Lindblom, Karin

AU - Onnerfjord, Patrik

AU - Jonsson, Björn-Anders

AU - Tegner, Yelverton

AU - Sasaki, Takako

AU - Struglics, André

AU - Lohmander, Stefan

AU - Dahl, Niklas

AU - Heinegård, Dick

AU - Aspberg, Anders

PY - 2010

Y1 - 2010

N2 - Osteochondritis dissecans is a disorder in which fragments of articular cartilage and subchondral bone dislodge from the joint surface. We analyzed a five-generation family in which affected members had autosomal-dominant familial osteochondritis dissecans. A genome-wide linkage analysis identified aggrecan (ACAN) as a prime candidate gene for the disorder. Sequence analysis of ACAN revealed heterozygosity for a missense mutation (c.6907G > A) in affected individuals, resulting in a p.V2303M amino acid substitution in the aggrecan G3 domain C-type lectin, which mediates interactions with other proteins in the cartilage extracellular matrix. Binding studies with recombinant mutated and wild-type G3 proteins showed loss of fibulin-1, fibulin-2, and tenascin-R interactions for the V2303M protein. Mass spectrometric analyses of aggrecan purified from patient cartilage verified that V2303M aggrecan is produced and present in the tissue. Our results provide a molecular mechanism for the etiology of familial osteochondritis dissecans and show the importance of the aggrecan C-type lectin interactions for cartilage function in vivo.

AB - Osteochondritis dissecans is a disorder in which fragments of articular cartilage and subchondral bone dislodge from the joint surface. We analyzed a five-generation family in which affected members had autosomal-dominant familial osteochondritis dissecans. A genome-wide linkage analysis identified aggrecan (ACAN) as a prime candidate gene for the disorder. Sequence analysis of ACAN revealed heterozygosity for a missense mutation (c.6907G > A) in affected individuals, resulting in a p.V2303M amino acid substitution in the aggrecan G3 domain C-type lectin, which mediates interactions with other proteins in the cartilage extracellular matrix. Binding studies with recombinant mutated and wild-type G3 proteins showed loss of fibulin-1, fibulin-2, and tenascin-R interactions for the V2303M protein. Mass spectrometric analyses of aggrecan purified from patient cartilage verified that V2303M aggrecan is produced and present in the tissue. Our results provide a molecular mechanism for the etiology of familial osteochondritis dissecans and show the importance of the aggrecan C-type lectin interactions for cartilage function in vivo.

U2 - 10.1016/j.ajhg.2009.12.018

DO - 10.1016/j.ajhg.2009.12.018

M3 - Journal article

C2 - 20137779

VL - 86

SP - 126

EP - 137

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

SN - 0002-9297

IS - 2

ER -

ID: 18476033