|
Multiple Epiphyseal Dysplasia
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Multiple epiphyseal dysplasia (EDM5) is a genetic skeletal condition and a classic example of an intracellular protein aggregation disease, whereby mutant matrilin-3 forms large insoluble aggregates in the ER lumen, resulting in a specific 'disease signature' of increased expression of chaperones and foldases, and alternative splicing of the UPR effector XBP1.
|
31260448 |
2019 |
|
Multiple Epiphyseal Dysplasia
|
0.500 |
Biomarker
|
disease |
BEFREE |
Our data highlights the importance of detection and careful characterization of intragenic duplication CNVs, presenting them as a novel and very rare genetic mechanism in IFT81-related Jeune syndrome and MATN3-related MED.
|
30080953 |
2018 |
|
Multiple Epiphyseal Dysplasia
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
We transfected these contructs into the COS-1 or MCT cells, and the results revealed that the HOA-related matrilin-3 mutation (T298M) leads to a high expression level of growth arrest DNA damage-inducible gene 153 (GADD153, also known as CHOP; an endoplasmic reticulum stress marker), as shown by western blot analysis and does not significantly affect protein secretion, as shown by immunofluorescence staining; however, osteochondroplasia, i.e., MED-related (R116W) and SEMD-related (C299S) mutations lead to both high levels of GADD153 expression and protein trafficking into the cytoplasm and form multiple vacuoles in cells, which in turn leads to insufficient protein secretion.
|
26499313 |
2015 |
|
Multiple Epiphyseal Dysplasia
|
0.500 |
Biomarker
|
disease |
BEFREE |
We demonstrate that Armet and Creld2 are genotype-specific ER stress response proteins with substrate specificities, and that aggregation of mutant matrilin-3 is a key disease trigger in MED that could be exploited as a potential therapeutic target.
|
23956175 |
2013 |
|
Multiple Epiphyseal Dysplasia
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
PSACH and the largest proportion of autosomal dominant MED (AD-MED) results from mutations in cartilage oligomeric matrix protein (COMP); however, AD-MED is genetically heterogenous and can also result from mutations in matrilin-3 (MATN3) and type IX collagen (COL9A1, COL9A2, and COL9A3).
|
21922596 |
2012 |
|
Multiple Epiphyseal Dysplasia
|
0.500 |
Biomarker
|
disease |
BEFREE |
The study confirms that MATN3 and COMP are the genes most frequently responsible for MED and that subtle radiographic signs may give precious indications on which gene(s) should be prioritized for mutational screening in a given individual.
|
21965141 |
2011 |
|
Multiple Epiphyseal Dysplasia
|
0.500 |
Biomarker
|
disease |
GENOMICS_ENGLAND |
Type IX collagen gene mutations can result in multiple epiphyseal dysplasia that is associated with osteochondritis dissecans and a mild myopathy.
|
20358595 |
2010 |
|
Multiple Epiphyseal Dysplasia
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Some forms of MED result from mutations in the gene encoding the cartilage structural protein matrilin-3 (MATN3).
|
18205203 |
2008 |
|
Multiple Epiphyseal Dysplasia
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Mutations in matrilin-3 result in multiple epiphyseal dysplasia, which is characterized by delayed and irregular bone growth and early onset osteoarthritis.
|
17881354 |
2007 |
|
Multiple Epiphyseal Dysplasia
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Light microscopy of cartilage from an MED patient with a MATN3 mutation showed the presence of intracellular material within the chondrocytes, whilst the overall matrix appeared normal.
|
16287128 |
2005 |
|
Multiple Epiphyseal Dysplasia
|
0.500 |
Biomarker
|
disease |
GENOMICS_ENGLAND |
Light microscopy of cartilage from an MED patient with a MATN3 mutation showed the presence of intracellular material within the chondrocytes, whilst the overall matrix appeared normal.
|
16287128 |
2005 |
|
Multiple Epiphyseal Dysplasia
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
The disorders include "classic MED" (Ribbing and Fairbank types): MED that is caused by mutations in the cartilage oligomeric matrix protein (COMP), type IX collagen, and matrilin 3 genes (MATN3); and MED with multilayered patella, brachydactyly, and clubbed feet resultant from mutations in gene defect diastrophic dysplasia (DTDST).
|
15503005 |
2005 |
|
Multiple Epiphyseal Dysplasia
|
0.500 |
Biomarker
|
disease |
BEFREE |
Novel and recurrent mutations clustered in the von Willebrand factor A domain of MATN3 in multiple epiphyseal dysplasia.
|
15459972 |
2004 |
|
Multiple Epiphyseal Dysplasia
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
We have identified disease-causing mutations in the gene encoding matrilin-3, an extracellular matrix protein, in seven families with autosomal dominant MED.
|
14994237 |
2004 |
|
Multiple Epiphyseal Dysplasia
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Linkage and mutation analysis of matrilin-3 (MATN-3) revealed a new pathogenic mutation confirming that BHMED is indeed a distinct disease entity among MED and MED-like disorders.
|
12884427 |
2003 |
|
Multiple Epiphyseal Dysplasia
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
We have identified two different missense mutations in the exon encoding the von Willebrand factor A (vWFA) domain of matrilin-3 in two unrelated families with MED (EDM5).
|
11479597 |
2001 |
|
Multiple Epiphyseal Dysplasia
|
0.500 |
Biomarker
|
disease |
BEFREE |
Mutations causing MED have now been identified in five other genes (COL9A1, COL9A2, COL9A3, DTDST, and MATN3), making MED one of the most genetically heterogeneous disorders.
|
11891674 |
2001 |
|
Multiple Epiphyseal Dysplasia
|
0.500 |
Biomarker
|
disease |
HPO |
|
|
|