The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
Digenic inheritance of an SMCHD1 mutation and an FSHD-permissive D4Z4 allele causes facioscapulohumeral muscular dystrophy type 2
Open accessAbstract
Facioscapulohumeral dystrophy (FSHD) is characterized by chromatin relaxation of the D4Z4 macrosatellite array on chromosome 4 and expression of the D4Z4-encoded DUX4 gene in skeletal muscle. The more common form, autosomal dominant FSHD1, is caused by contraction of the D4Z4 array, whereas the genetic determinants and inheritance of D4Z4 array contraction–independent FSHD2 are unclear. Here, we show that mutations in SMCHD1 (encoding structural maintenance of chromosomes flexible hinge domain containing 1) on chromosome 18 reduce SMCHD1 protein levels and segregate with genome-wide D4Z4 CpG hypomethylation in human kindreds. FSHD2 occurs in individuals who inherited both the SMCHD1 mutation and a normal-sized D4Z4 array on a chromosome 4 haplotype permissive for DUX4 expression. Reducing SMCHD1 levels in skeletal muscle results in D4Z4 contraction–independent DUX4 expression. Our study identifies SMCHD1 as an epigenetic modifier of the D4Z4 metastable epiallele and as a causal genetic determinant of FSHD2 and possibly other human diseases subject to epigenetic regulation.
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Metastable epialleles in mammals
Rakyan, V. K., Blewitt, M. E., Druker, R., Preis, J. I., & Whitelaw, E. (2002) · Trends in Genetics · doi:10.1016/s0168-9525(02)02709-9 · Cited by 499
Blewitt, M. E., Gendrel, A.-V., Pang, Z., Sparrow, D. B., Whitelaw, N., Craig, J. M., Apedaile, A., Hilton, D. J., Dunwoodie, S. L., Brockdorff, N., et al. (2008) · Nature Genetics · doi:10.1038/ng.142 · Cited by 366
An N -ethyl- N -nitrosourea screen for genes involved in variegation in the mouse
Blewitt, M. E., Vickaryous, N. K., Hemley, S. J., Ashe, A., Bruxner, T. J., Preis, J. I., Arkell, R., & Whitelaw, E. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409375102 · Cited by 186
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Self-citationSomatic mosaicism: implications for disease and transmission genetics
Campbell, I. M., Shaw, C. A., Stankiewicz, P., & Lupski, J. R. (2015) · Trends in Genetics · doi:10.1016/j.tig.2015.03.013 · Cited by 296
A Nondegenerate Code of Deleterious Variants in Mendelian Loci Contributes to Complex Disease Risk
Blair, D. R., Lyttle, C. S., Mortensen, J. M., Bearden, C. F., Jensen, A. B., Khiabanian, H., Melamed, R., Rabadan, R., Bernstam, E. V., Brunak, S., et al. (2013) · Cell · doi:10.1016/j.cell.2013.08.030 · Cited by 215
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Metadata
- Authors
- Lemmers, R. J. L. F., Tawil, R., Petek, L. M., Balog, J., Block, G. J., Santen, G. W. E., Amell, A. M., van der Vliet, P. J., Almomani, R., Straasheijm, K. R., Krom, Y. D., Klooster, R., Sun, Y., den Dunnen, J. T., Helmer, Q., Donlin-Smith, C. M., Padberg, G. W., van Engelen, B. G. M., de Greef, J. C., Aartsma-Rus, A. M., Frants, R. R., de Visser, M., Desnuelle, C., Sacconi, S., Filippova, G. N., Bakker, B., Bamshad, M. J., Tapscott, S. J., Miller, D. G., & van der Maarel, S. M.
- Venue
- Nature Genetics
- Published
- 2012-11-11
- Volume
- 44
- Issue
- 12
- Pages
- 1370-1374
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2018380248
- Cited by
- 660
- References
- 3
- FWCI
- 16.03
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: Digenic inheritance of an SMCHD1 mutation and an FSHD-permissive D4Z4 allele causes facioscapulohumeral muscular dystrophy type 2. https://app.cochat.ai/papers/10.1038/ng.2454
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- Lemmers, R. J. L. F., Tawil, R., Petek, L. M., Balog, J., Block, G. J., Santen, G. W. E., Amell, A. M., van der Vliet, P. J., Almomani, R., Straasheijm, K. R., Krom, Y. D., Klooster, R., Sun, Y., den Dunnen, J. T., Helmer, Q., Donlin-Smith, C. M., Padberg, G. W., van Engelen, B. G. M., de Greef, J. C., . . . van der Maarel, S. M. (2012). Digenic inheritance of an SMCHD1 mutation and an FSHD-permissive D4Z4 allele causes facioscapulohumeral muscular dystrophy type 2. Nature Genetics. https://doi.org/10.1038/ng.2454
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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