Missense mutations in the beta strands of the single A-domain of matrilin-3 result in multiple epiphyseal dysplasia.
نویسندگان
چکیده
G C Jackson, F S Barker, E Jakkula, M Czarny-Ratajczak, O Mäkitie, W G Cole, M J Wright, S F Smithson, M Suri, P Rogala, G R Mortier, C Baldock, A Wallace, R Elles, L Ala-Kokko, M D Briggs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
منابع مشابه
Multiple epiphyseal dysplasia mutations in MATN3 cause misfolding of the A-domain and prevent secretion of mutant matrilin-3
Multiple epiphyseal dysplasia (MED) is a relatively common skeletal dysplasia that can present in childhood with a variable phenotype of short stature and pain and stiffness in the large joints, and often progresses to early-onset osteoarthritis in adulthood. Mutations in the matrilin-3 gene (MATN3) have recently been shown to underlie some forms of autosomal dominant MED. To date all MED mutat...
متن کاملLoss of matrilin 1 does not exacerbate the skeletal phenotype in a mouse model of multiple epiphyseal dysplasia caused by a Matn3 V194D mutation
OBJECTIVE Mutations in matrilin 3 can result in multiple epiphyseal dysplasia (MED), a disease characterized by delayed and irregular bone growth and early-onset osteoarthritis. Although intracellular retention of the majority of mutant matrilin 3 was previously observed in a murine model of MED caused by a Matn3 V194D mutation, some mutant protein was secreted into the extracellular matrix. Th...
متن کاملMultiple functions of the von Willebrand Factor A domain in matrilins: secretion, assembly, and proteolysis
The von Willebrand Factor A (vWF A) domain is one of the most widely distributed structural modules in cell-matrix adhesive molecules such as intergrins and extracellular matrix proteins. Mutations in the vWF A domain of matrilin-3 cause multiple epiphyseal dysplasia (MED), however the pathological mechanism remains to be determined. Previously we showed that the vWF A domain in matrilin-1 medi...
متن کاملStructural and functional characterization of recombinant matrilin-3 A-domain and implications for human genetic bone diseases.
Mutations in matrilin-3 result in multiple epiphyseal dysplasia, which is characterized by delayed and irregular bone growth and early onset osteoarthritis. The majority of disease-causing mutations are located within the beta-sheet of the single A-domain of matrilin-3, suggesting that they disrupt the structure and/or function of this important domain. Indeed, the expression of mutant matrilin...
متن کاملMultiple functions of the first EGF domain in matrilin-3: Secretion and endoplasmic reticulum stress.
Mutations in matrilin-3 are associated with common skeletal diseases, such as hand osteoarthritis (HOA), as well as rare chondrodysplasias, such as multiple epiphyseal dysplasia (MED) and spondyloepimetaphyseal dysplasia (SEMD). In the present study, we constructed the mutations R116W [at the von Willebrand factor, type A (vWFA) domain], T298M [at the first epidermal growth factor (EGF) domain]...
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ورودعنوان ژورنال:
- Journal of medical genetics
دوره 41 1 شماره
صفحات -
تاریخ انتشار 2004