RGD Reference Report - Mutations in MMP9 and MMP13 determine the mode of inheritance and the clinical spectrum of metaphyseal anadysplasia. - Rat Genome Database

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Mutations in MMP9 and MMP13 determine the mode of inheritance and the clinical spectrum of metaphyseal anadysplasia.

Authors: Lausch, Ekkehart  Keppler, Romy  Hilbert, Katja  Cormier-Daire, Valerie  Nikkel, Sarah  Nishimura, Gen  Unger, Sheila  Spranger, Jürgen  Superti-Furga, Andrea  Zabel, Bernhard 
Citation: Lausch E, etal., Am J Hum Genet. 2009 Aug;85(2):168-78. doi: 10.1016/j.ajhg.2009.06.014. Epub 2009 Jul 16.
RGD ID: 13204811
Pubmed: PMID:19615667   (View Abstract at PubMed)
PMCID: PMC2725238   (View Article at PubMed Central)
DOI: DOI:10.1016/j.ajhg.2009.06.014   (Journal Full-text)

The matrix metalloproteinases MMP9 and MMP13 catalyze the degradation of extracellular matrix (ECM) components in the growth plate and at the same time cleave and release biologically active molecules stored in the ECM, such as VEGFA. In mice, ablation of Mmp9, Mmp13, or both Mmp9 and Mmp13 causes severe distortion of the metaphyseal growth plate. We report that mutations in either MMP9 or MMP13 are responsible for the human disease metaphyseal anadysplasia (MAD), a heterogeneous group of disorders for which a milder recessive variant and a more severe dominant variant are known. We found that recessive MAD is caused by homozygous loss of function of either MMP9 or MMP13, whereas dominant MAD is associated with missense mutations in the prodomain of MMP13 that determine autoactivation of MMP13 and intracellular degradation of both MMP13 and MMP9, resulting in a double enzymatic deficiency.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Metaphyseal Anadysplasia  IAGP 13204811DNA:missense mutations: :p.F55S more ...RGD 
Metaphyseal Anadysplasia  IAGP 13204811DNA:missense mutations: :p.M1K (c.21T>A)(human)RGD 
Metaphyseal Anadysplasia  ISOMMP13 (Homo sapiens)13204811; 13204811DNA:missense mutations: :p.F55S more ...RGD 
Metaphyseal Anadysplasia  ISOMMP9 (Homo sapiens)13204811; 13204811DNA:missense mutations: :p.M1K (c.21T>A)(human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mmp13  (matrix metallopeptidase 13)
Mmp9  (matrix metallopeptidase 9)

Genes (Mus musculus)
Mmp13  (matrix metallopeptidase 13)
Mmp9  (matrix metallopeptidase 9)

Genes (Homo sapiens)
MMP13  (matrix metallopeptidase 13)
MMP9  (matrix metallopeptidase 9)


Additional Information