A new subtype of brachydactyly type B caused by point mutations in the bone morphogenetic protein antagonist NOGGIN

Basit Öğe Kaydı
dc.contributor.authorLehmann, K.
dc.contributor.authorSeemann, Petra
dc.contributor.authorSılan, Fatma
dc.contributor.authorGoecke, Tim O.
dc.contributor.authorIrgang, S.
dc.contributor.authorKjaer, K.W.
dc.contributor.authorMundlos, Stefan
dc.date.accessioned2020-04-30T22:38:44Z
dc.date.available2020-04-30T22:38:44Z
dc.date.issued2007
dc.departmentDÜ, Tıp Fakültesi, Dahili Tıp Bilimleri Bölümüen_US
dc.descriptionWilkie, Andrew/0000-0002-2972-5481; Seemann, Petra/0000-0002-6056-6669; Dathe, Katarina/0000-0002-8674-5817en_US
dc.descriptionWOS: 000248540400018en_US
dc.descriptionPubMed: 17668388en_US
dc.description.abstract(B) under bar rachy (d) under bar actyly type B (BDB) is characterized by terminal deficiency of fingers and toes, which is caused by heterozygous truncating mutations in the receptor tyrosine kinase-like orphan receptor 2 (ROR2) in the ma ority of patients n a subset of ROR2-negative patients with BDB, clinically defined by the additional occurrence of proximal symphalangism and carpal synostosis, we identified six different point mutations (P35A, P35S, A36p, E48K, R167G, and P187S) in the bone morphogenetic protein (BMP) antagonist NOGGIN (NOG). In contrast to previously described loss-of-function mutations in NOG, which are known to cause a range of conditions associated with abnormal joint formation but without BD13, the newly identified BDB mutations do not indicate a major loss of function, as suggested by calculation of free-binding energy of the modeled NOG-GDF5 complex and functional analysis of the micromass culture system. Rather, they presumably alter NOG's ability to bind to BMPs and growth-differentiation factors (GDFs) in a subtle way, thus disturbing the intricate balance of BMP signaling. The combined features observed in this phenotypic subtype of BDB argue for a functional connection between BMP and ROR2 signaling and support previous findings of a modulating effect of ROR2 on the BMP-receptor pathway through the formation of a heteromeric complex of the receptors at the cell surface.en_US
dc.description.sponsorshipWellcome TrustWellcome Trusten_US
dc.identifier.doi10.1086/519697en_US
dc.identifier.endpage396en_US
dc.identifier.issn0002-9297
dc.identifier.issue2en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage388en_US
dc.identifier.urihttps://doi.org/10.1086/519697
dc.identifier.urihttps://hdl.handle.net/20.500.12684/2417
dc.identifier.volume81en_US
dc.identifier.wosWOS:000248540400018en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakPubMeden_US
dc.indekslendigikaynakScopusen_US
dc.language.isoenen_US
dc.publisherUniv Chicago Pressen_US
dc.relation.ispartofAmerican Journal Of Human Geneticsen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.titleA new subtype of brachydactyly type B caused by point mutations in the bone morphogenetic protein antagonist NOGGINen_US
dc.typeArticleen_US

Dosyalar

Orijinal paket
Listeleniyor 1 - 1 / 1
Küçük Resim
İsim:
2417.pdf
Boyut:
504.92 KB
Biçim:
Adobe Portable Document Format
Açıklama:
Tam Metin / Full Text
İndir

Koleksiyon

WoS İndeksli Yayınlar Koleksiyonu
Makale Koleksiyonu
PubMed İndeksli Yayınlar Koleksiyonu
Scopus İndeksli Yayınlar Koleksiyonu