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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
agricultural and biological sciences
Loss of the BMP antagonist, SMOC-1, causes Ophthalmo-acromelic (Waardenburg anophthalmia) syndrome in humans and mice
PLoS Genetics, Volume 7, No. 7, Article e1002114, Year 2011
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Description
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. © 2011 Rainger et al.
Authors & Co-Authors
Rainger, Joe
United Kingdom, Edinburgh
Western General Hospital
van Beusekom, Ellen
Netherlands, Nijmegen
Radboud Institute for Molecular Life Sciences
Ramsay, Jacqueline K.
United Kingdom, Edinburgh
Western General Hospital
McKie, Lisa
United Kingdom, Edinburgh
Western General Hospital
Al-Gazali, Lihadh I.
United Arab Emirates, Al Ain
United Arab Emirates University
Pallotta, Rosanna
Italy, Chieti
University of G. D'annunzio Chieti and Pescara
Saponari, Anita
Italy, Chieti
University of G. D'annunzio Chieti and Pescara
Branney, Peter A.
United Kingdom, Edinburgh
Western General Hospital
Fisher, Malcolm E.
United Kingdom, Edinburgh
Western General Hospital
Morrison, Harris
United Kingdom, Edinburgh
Western General Hospital
Bicknell, Louise S.
United Kingdom, Edinburgh
Western General Hospital
Gautier, Philippe
United Kingdom, Edinburgh
Western General Hospital
Perry, Paul
United Kingdom, Edinburgh
Western General Hospital
Sokhi, Kishan
United Kingdom, Edinburgh
Western General Hospital
United Kingdom, Edinburgh
The University of Edinburgh
Sexton, David
United Kingdom, Edinburgh
Western General Hospital
Bardakjian, Tanya
United States, Philadelphia
Albert Einstein Medical Center
Schneider, Adele S.
United States, Philadelphia
Albert Einstein Medical Center
Elçioǧlu, Nursel H.
Turkey, Istanbul
Marmara Üniversitesi Tip Fakültesi
Ozkinay, Ferda
Turkey, Izmir
Ege Üniversitesi
Koenig, Rainer König
Germany, Frankfurt am Main
Goethe-universität Frankfurt am Main
Megarbane, Andre
Lebanon, Beirut
Université Saint-joseph de Beyrouth
Semerci, C. Nur
Turkey, Denizli
Pamukkale Üniversitesi
Khan, Ayesha
Pakistan, Rawalpindi
Al-shifa Trust Eye Hospital
Zafar, Saemah
Pakistan, Rawalpindi
Al-shifa Trust Eye Hospital
Hennekam, Raoul C.M.
Netherlands, Amsterdam
Universiteit Van Amsterdam
Sousa, Sérgio B.
Portugal, Coimbra
Centro Hospitalar e Universitário de Coimbra
Ramos, Lina
Portugal, Coimbra
Centro Hospitalar e Universitário de Coimbra
Garavelli, Livia
Italy, Reggio Emilia
Azienda Ospedaliera Santa Maria Nuova Di Reggio Emilia
Superti-Furga, Andrea
Switzerland, Lausanne
Université de Lausanne Unil
Wischmeijer, Anita
Italy, Reggio Emilia
Azienda Ospedaliera Santa Maria Nuova Di Reggio Emilia
Jackson, Ian James
United Kingdom, Edinburgh
Western General Hospital
Gillessen-Kaesbach, G.
Germany, Lubeck
Universität zu Lübeck
Brunner, Han G.
Netherlands, Nijmegen
Radboud Institute for Molecular Life Sciences
Wieczorek, Dagmar
Germany, Essen
Universitätsklinikum Essen
van Bokhoven, Hans
Netherlands, Nijmegen
Radboud Institute for Molecular Life Sciences
Fitzpatrick, David R.
United Kingdom, Edinburgh
Western General Hospital
Statistics
Citations: 83
Authors: 36
Affiliations: 18
Identifiers
Doi:
10.1371/journal.pgen.1002114
e-ISSN:
15537404
Research Areas
Cancer
Genetics And Genomics
Health System And Policy