{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T22:27:44Z","timestamp":1790375264646,"version":"4.1.0"},"reference-count":12,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2014,3,19]],"date-time":"2014-03-19T00:00:00Z","timestamp":1395187200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2014,5]]},"abstract":"<jats:sec><jats:label\/><jats:p>Metaphyseal dysplasia, Spahr type (MDST; OMIM 250400) was described in 1961 based on the observation of four children in one family who had rickets\u2010like 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\u2010dimensional models of the affected protein. The MDST phenotype is associated with moderate short stature and knee pain in adults, while extra\u2010skeletal complications are not observed. The sequencing showed that MDST segregated with a c.619T&gt;G single nucleotide transversion in <jats:italic>MMP13<\/jats:italic>. The predicted non\u2010conservative amino acid substitution, p.Trp207Gly, disrupts a crucial hydrogen bond in the calcium\u2010binding region of the catalytic domain of the matrix metalloproteinase, MMP13. The MDST phenotype is associated with recessive <jats:italic>MMP13<\/jats:italic> mutations, confirming the importance of this metalloproteinase in the metaphyseal growth plate. Dominant <jats:italic>MMP13<\/jats:italic> mutations have been associated with metaphyseal anadysplasia (OMIM 602111), while a single child homozygous for a <jats:italic>MMP13<\/jats:italic> mutation had been previously diagnosed as \u201crecessive metaphyseal anadysplasia,\u201d 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\u2010system conditions (such as cartilage\u2010hair hypoplasia; OMIM # 250250) and to give precise recurrence risks and prognosis. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.36431","type":"journal-article","created":{"date-parts":[[2014,3,19]],"date-time":"2014-03-19T18:36:11Z","timestamp":1395254171000},"page":"1175-1179","source":"Crossref","is-referenced-by-count":20,"title":["<i>MMP13<\/i> mutations are the cause of recessive metaphyseal dysplasia, Spahr type"],"prefix":"10.1002","volume":"164","author":[{"given":"Luisa","family":"Bonaf\u00e9","sequence":"first","affiliation":[{"name":"Division of Molecular Pediatrics Lausanne University Hospital Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinlong","family":"Liang","sequence":"additional","affiliation":[{"name":"BGI\u2010Shenzhen Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria W.","family":"Gorna","sequence":"additional","affiliation":[{"name":"CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingyan","family":"Zhang","sequence":"additional","affiliation":[{"name":"BGI\u2010Shenzhen Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russia","family":"Ha\u2010Vinh","sequence":"additional","affiliation":[{"name":"Division of Molecular Pediatrics Lausanne University Hospital Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Belinda","family":"Campos\u2010Xavier","sequence":"additional","affiliation":[{"name":"Division of Molecular Pediatrics Lausanne University Hospital Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheila","family":"Unger","sequence":"additional","affiliation":[{"name":"Medical Genetics Service Lausanne University Hospital Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques S.","family":"Beckmann","sequence":"additional","affiliation":[{"name":"Medical Genetics Service Lausanne University Hospital Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antony","family":"Le B\u00e9chec","sequence":"additional","affiliation":[{"name":"Vital\u2010IT\u2014High Performance Computing Center Swiss Institute of Bioinformatics University of Lausanne Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Stevenson","sequence":"additional","affiliation":[{"name":"Vital\u2010IT\u2014High Performance Computing Center Swiss Institute of Bioinformatics 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P\u00e9diatrie Sion Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Superti\u2010Furga","sequence":"additional","affiliation":[{"name":"Division of Molecular Pediatrics Lausanne University Hospital Lausanne Switzerland"},{"name":"Department of Pediatrics Lausanne University Hospital, University of Lausanne Lausanne 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