Titre
MMP13 mutations are the cause of recessive metaphyseal dysplasia, Spahr type.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Auteur(s)
Bonafé, L.
Auteure/Auteur
Liang, J.
Auteure/Auteur
Gorna, M.W.
Auteure/Auteur
Zhang, Q.
Auteure/Auteur
Ha-Vinh, R.
Auteure/Auteur
Campos-Xavier, A.B.
Auteure/Auteur
Unger, S.
Auteure/Auteur
Beckmann, J.S.
Auteure/Auteur
Le Béchec, A.
Auteure/Auteur
Stevenson, B.
Auteure/Auteur
Giedion, A.
Auteure/Auteur
Liu, X.
Auteure/Auteur
Superti-Furga, G.
Auteure/Auteur
Wang, W.
Auteure/Auteur
Spahr, A.
Auteure/Auteur
Superti-Furga, A.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1552-4833
Statut éditorial
Publié
Date de publication
2014
Volume
164
Numéro
5
Première page
1175
Dernière page/numéro d’article
1179
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article Publication Status: ppublishPDF: Research Article
Résumé
Metaphyseal dysplasia, Spahr type (MDST; OMIM 250400) was described in 1961 based on the observation of four children in one family who had rickets-like metaphyseal changes but normal blood chemistry and moderate short stature. Its molecular basis and nosologic status remained unknown. We followed up on those individuals and diagnosed the disorder in an additional member of the family. We used exome sequencing to ascertain the underlying mutation and explored its consequences on three-dimensional models of the affected protein. The MDST phenotype is associated with moderate short stature and knee pain in adults, while extra-skeletal complications are not observed. The sequencing showed that MDST segregated with a c.619T>G single nucleotide transversion in MMP13. The predicted non-conservative amino acid substitution, p.Trp207Gly, disrupts a crucial hydrogen bond in the calcium-binding region of the catalytic domain of the matrix metalloproteinase, MMP13. The MDST phenotype is associated with recessive MMP13 mutations, confirming the importance of this metalloproteinase in the metaphyseal growth plate. Dominant MMP13 mutations have been associated with metaphyseal anadysplasia (OMIM 602111), while a single child homozygous for a MMP13 mutation had been previously diagnosed as "recessive metaphyseal anadysplasia," that we conclude is the same nosologic entity as MDST. Molecular confirmation of MDST allows distinction of it from dominant conditions (e.g., metaphyseal dysplasia, Schmid type; OMIM # 156500) and from more severe multi-system conditions (such as cartilage-hair hypoplasia; OMIM # 250250) and to give precise recurrence risks and prognosis. © 2014 Wiley Periodicals, Inc.
PID Serval
serval:BIB_AA520EFE4A1E
PMID
Date de création
2014-05-23T16:11:01.509Z
Date de création dans IRIS
2025-05-20T22:45:50Z