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Mutations in the cyclin family member FAM58A cause an X-linked dominant disorder characterized by syndactyly, telecanthus and anogenital and renal malformations

Abstract

We identified four girls with a consistent constellation of facial dysmorphism and malformations previously reported in a single mother–daughter pair. Toe syndactyly, telecanthus and anogenital and renal malformations were present in all affected individuals; thus, we propose the name 'STAR syndrome' for this disorder. Using array CGH, qPCR and sequence analysis, we found causative mutations in FAM58A on Xq28 in all affected individuals, suggesting an X-linked dominant inheritance pattern for this recognizable syndrome.

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Figure 1: Clinical and molecular characterization of STAR syndrome.

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Acknowledgements

We thank the research subjects and their families for their participation, generosity and patience. We thank G. Scherer for critical discussion, P. Hermanns and B. Rösler for help with cell cultures, and C. Lich for technical assistance. J.K. received funding from the Deutsche Forschungsgemeinschaft (grant no. Ko1850/6-1,6-2).

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Authors and Affiliations

Authors

Contributions

S.U. contributed to the clinical evalutation of cases, syndrome delineation and subject enrollment in the study. D.B. performed array CGH, mutation analysis and qPCR. W.B. performed mutation analysis on MYCN, SALL1 and SALL4 and FAM58A breakpoint cloning. F.J.K. performed co-immunoprecipitation studies. K. Buiting performed X-chromosome inactivation studies. S.K. and P.B. performed cell culture studies, siRNA knockdown experiments and proliferation assays, and contributed to the manuscript. J.B., F.B. and A.C. cloned expression constructs and performed RT-PCR. K. Borowski, K.K.-N., G.M., T.S.-M., B.S., D. Bartholdi, R.S., B.Z., and A.S.-F contributed to subject enrollment and clinical evaluation. S.U., D.B., J.B., F.J.K., K.Bu., S.K., P.B., R.S., G.M. and A.S.-F. also contributed to the manuscript. J.K. oversaw all aspects of the research and wrote major parts of the manuscript.

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Correspondence to Jürgen Kohlhase.

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Supplementary Note, Supplementary Methods, Supplementary Figures 1–6, Supplementary Table 1 (PDF 3653 kb)

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Unger, S., Böhm, D., Kaiser, F. et al. Mutations in the cyclin family member FAM58A cause an X-linked dominant disorder characterized by syndactyly, telecanthus and anogenital and renal malformations. Nat Genet 40, 287–289 (2008). https://doi.org/10.1038/ng.86

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