TY  - JOUR
A1  - Rainger, Joe
A1  - Beusekom, Ellen van
A1  - Ramsay, Jacqueline K.
A1  - McKie, Lisa
A1  - Al-Gazali, Lihadh
A1  - Pallotta, Rosanna
A1  - Saponari, Anita
A1  - Branney, Peter
A1  - Fisher, Malcolm
A1  - Morrison, Harris
A1  - Bicknell, Louise
A1  - Gautier, Philippe
A1  - Perry, Paul
A1  - Sokhi, Kishan
A1  - Sexton, David
A1  - Bardakjian, Tanya M.
A1  - Schneider, Adele S.
A1  - Elcioglu, Nursel
A1  - Ozkinay, Ferda
A1  - Koenig, Rainer
A1  - Mégarbané, Andre
A1  - Semerci, C. Nur
A1  - Khan, Ayesha
A1  - Zafar, Saemah
A1  - Hennekam, Raoul C.
A1  - Sousa, Sérgio B.
A1  - Ramos, Lina
A1  - Garavelli, Livia
A1  - Furga, Andrea Superti
A1  - Wischmeijer, Anita
A1  - Jackson, Ian J.
A1  - Gillessen-Kaesbach, Gabriele Gertrud
A1  - Brunner, Han G.
A1  - Wieczorek, Dagmar
A1  - Bokhoven, Hans van
A1  - FitzPatrick, David R.
T1  - Loss of the BMP antagonist, SMOC-1, causes Ophthalmo-Acromelic (Waardenburg Anophthalmia) syndrome in humans and mice
T2  - PLoS Genetics, volume 7, issue 7, e1002114 (2011)
N2  - Ophthalmo-acromelic syndrome (OAS), also known as Waardenburg Anophthalmia syndrome, is defined by the combination of eye malformations, most commonly bilateral anophthalmia, with post-axial oligosyndactyly. Homozygosity mapping and subsequent targeted mutation analysis of a locus on 14q24.2 identified homozygous mutations in SMOC1 (SPARC-related modular calcium binding 1) in eight unrelated families. Four of these mutations are nonsense, two frame-shift, and two missense. The missense mutations are both in the second Thyroglobulin Type-1 (Tg1) domain of the protein. The orthologous gene in the mouse, Smoc1, shows site- and stage-specific expression during eye, limb, craniofacial, and somite development. We also report a targeted pre-conditional gene-trap mutation of Smoc1 (Smoc1tm1a) that reduces mRNA to ~10% of wild-type levels. This gene-trap results in highly penetrant hindlimb post-axial oligosyndactyly in homozygous mutant animals (Smoc1tm1a/tm1a). Eye malformations, most commonly coloboma, and cleft palate occur in a significant proportion of Smoc1tm1a/tm1a embryos and pups. Thus partial loss of Smoc-1 results in a convincing phenocopy of the human disease. SMOC-1 is one of the two mammalian paralogs of Drosophila Pentagone, an inhibitor of decapentaplegic. The orthologous gene in Xenopus laevis, Smoc-1, also functions as a Bone Morphogenic Protein (BMP) antagonist in early embryogenesis. Loss of BMP antagonism during mammalian development provides a plausible explanation for both the limb and eye phenotype in humans and mice.
Y1  - 2011
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/22675
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30-91201
SN  - 1553-7404
VL  - 7
IS  - (7): e1002114
ER  -