Correction: Loss of the BMP Antagonist, SMOC-1, Causes Ophthalmo-Acromelic (Waardenburg Anophthalmia) Syndrome in Humans and Mice.
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ABSTRACT:
SUBMITTER: Rainger J
PROVIDER: S-EPMC6306194 | biostudies-literature | 2018 Dec
REPOSITORIES: biostudies-literature
Publications
Correction: Loss of the BMP Antagonist, SMOC-1, Causes Ophthalmo-Acromelic (Waardenburg Anophthalmia) Syndrome in Humans and Mice.
Rainger Joe J van Beusekom Ellen E Ramsay Jacqueline K JK McKie Lisa L Al-Gazali Lihadh L Pallotta Rosanna R Saponari Anita A Branney Peter P Fisher Malcolm M Morrison Harris H Bicknell Louise L Gautier Philippe P Perry Paul P Sokhi Kishan K Sexton David D Bardakjian Tanya M TM Schneider Adele S AS Elcioglu Nursel N Ozkinay Ferda F Koenig Rainer R Mégarbané Andre A Semerci C Nur CN Khan Ayesha A Zafar Saemah S Hennekam Raoul R Sousa Sérgio B SB Ramos Lina L Garavelli Livia L Furga Andrea Superti AS Wischmeijer Anita A Jackson Ian J IJ Gillessen-Kaesbach Gabriele G Brunner Han G HG Wieczorek Dagmar D van Bokhoven Hans H FitzPatrick David R DR
PLoS genetics 20181226 12
[This corrects the article DOI: 10.1371/journal.pgen.1002114.]. ...[more]
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Project 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 (Smoc1(tm1a)) that reduces mRNA to ?10% of wild-type levels. This gene-trap results in highly penetrant hindlimb post-axial oligosyndactyly in homozygous mutant animals (Smoc1(tm1a/tm1a)). Eye malformations, most commonly coloboma, and cleft palate occur in a significant proportion of Smoc1(tm1a/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.
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