Basit öğe kaydını göster

dc.contributor.authorHellemans, Jan
dc.contributor.authorSimon, Marleen
dc.contributor.authorDheedene, Annelies
dc.contributor.authorAlanay, Yasemin
dc.contributor.authorMihci, Ercan
dc.contributor.authorRifai, Laila
dc.contributor.authorSefiani, Abdelaziz
dc.contributor.authorvan Bever, Yolande
dc.contributor.authorMeradji, Morteza
dc.contributor.authorSuperti-Furga, Andrea
dc.contributor.authorMortier, Geert
dc.date.accessioned2019-12-10T10:38:38Z
dc.date.available2019-12-10T10:38:38Z
dc.date.issued2009
dc.identifier.issn0002-9297
dc.identifier.urihttps://doi.org/10.1016/j.ajhg.2009.11.005
dc.identifier.urihttp://hdl.handle.net/11655/14069
dc.description.abstractSpondylo-megaepiphyseal-metaphyseal dysplasia (SMMD) is a rare skeletal dysplasia with only a few cases reported in the literature. Affected individuals have a disproportionate short stature with a short and stiff neck and trunk. The limbs appear relatively long and may show flexion contractures of the distal joints. The most remarkable radiographic features are the delayed and impaired ossification of the vertebral bodies as well as the presence of large epiphyseal ossification centers and wide growth plates in the long tubular bones. Numerous pseudoepiphyses of the short tubular bones in hands and feet are another remarkable feature of the disorder. Genome wide homozygosity mapping followed by a candidate gene approach resulted in the elucidation of the genetic cause in three new consanguineous families with SMMD. Each proband was homozygous for a different inactivating mutation in NKX3-2, a homeobox-containing gene located on chromosome 4p15.33. Striking similarities were found when comparing the vertebral ossification defects in SMMD patients with those observed in the Nkx3-2 null mice. Distinguishing features were the asplenia found in the mutant mice and the radiographic abnormalities in the limbs only observed in SMMD patients. The absence of the latter anomalies in the murine model may be due to the perinatal death of the affected animals. This study illustrates that NKX3-2 plays an important role in endochondral ossification of both the axial and appendicular skeleton in humans. In addition, it defines SMMD as yet another skeletal dysplasia with autosomal-recessive inheritance and a distinct phenotype.
dc.language.isoen
dc.publisherCell Press
dc.relation.isversionof10.1016/j.ajhg.2009.11.005
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectGenetics & Heredity
dc.titleHomozygous Inactivating Mutations In The Nkx3-2 Gene Result In Spondylo-Megaepiphyseal-Metaphyseal Dysplasia
dc.typeinfo:eu-repo/semantics/article
dc.typeinfo:eu-repo/semantics/publishedVersion
dc.relation.journalAmerican Journal Of Human Genetics
dc.contributor.departmentÇocuk Sağlığı ve Hastalıkları
dc.identifier.volume85
dc.identifier.issue6
dc.identifier.startpage916
dc.identifier.endpage922
dc.description.indexWoS
dc.description.indexScopus


Bu öğenin dosyaları:

Bu öğe aşağıdaki koleksiyon(lar)da görünmektedir.

Basit öğe kaydını göster