Gordon, Christopher T., Xue, Shifeng ORCID: 0000-0002-4668-5952, Yigit, Goekhan, Filali, Hicham ORCID: 0000-0003-3352-740X, Chen, Kelan ORCID: 0000-0003-1973-5405, Rosins, Nadine, Yoshiura, Koh-ichiro, Oufadem, Myriam, Beck, Tamara J., McGowan, Ruth, Magee, Alex C., Altmueller, Janine, Dion, Camille, Thiele, Holger, Gurzau, Alexandra D., Nuernberg, Peter, Meschede, Dieter, Muehlbauer, Wolfgang, Okamoto, Nobuhiko, Varghese, Vinod, Irving, Rachel, Sigaudy, Sabine, Williams, Denise, Ahmed, S. Faisal, Bonnard, Carine, Kong, Mung Kei, Ratbi, Ilham, Fejjal, Nawfal, Fikri, Meriem, Elalaoui, Siham Chafai, Reigstad, Hallvard, Bole-Feysot, Christine, Nitschke, Patrick, Ragge, Nicola, Levy, Nicolas, Tuncbilek, Goekhan, Teo, Audrey S. M., Cunningham, Michael L., Sefiani, Abdelaziz, Kayserili, Huelya, Murphy, James M., Chatdokmaiprai, Chalermpong, Hillmer, Axel M., Wattanasirichaigoon, Duangrurdee, Lyonnet, Stanislas ORCID: 0000-0001-5426-9417, Magdinier, Frederique ORCID: 0000-0002-0159-9559, Javed, Asif, Blewitt, Marnie E., Amiel, Jeanne, Wollnik, Bernd and Reversade, Bruno (2017). De novo mutations in SMCHD1 cause Bosma arhinia microphthalmia syndrome and abrogate nasal development. Nature Genet., 49 (2). S. 249 - 256. NEW YORK: NATURE PUBLISHING GROUP. ISSN 1546-1718

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Abstract

Bosma arhinia microphthalmia syndrome (BAMS) is an extremely rare and striking condition characterized by complete absence of the nose with or without ocular defects. We report here that missense mutations in the epigenetic regulator SMCHD1 mapping to the extended ATPase domain of the encoded protein cause BAMS in all 14 cases studied. All mutations were de novo where parental DNA was available. Biochemical tests and in vivo assays in Xenopus laevis embryos suggest that these mutations may behave as gain-of-function alleles. This finding is in contrast to the loss-of-function mutations in SMCHD1 that have been associated with facioscapulohumeral muscular dystrophy (FSHD) type 2. Our results establish SMCHD1 as a key player in nasal development and provide biochemical insight into its enzymatic function that may be exploited for development of therapeutics for FSHD.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Gordon, Christopher T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Xue, ShifengUNSPECIFIEDorcid.org/0000-0002-4668-5952UNSPECIFIED
Yigit, GoekhanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Filali, HichamUNSPECIFIEDorcid.org/0000-0003-3352-740XUNSPECIFIED
Chen, KelanUNSPECIFIEDorcid.org/0000-0003-1973-5405UNSPECIFIED
Rosins, NadineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yoshiura, Koh-ichiroUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Oufadem, MyriamUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beck, Tamara J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
McGowan, RuthUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Magee, Alex C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Altmueller, JanineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dion, CamilleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thiele, HolgerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gurzau, Alexandra D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nuernberg, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meschede, DieterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Muehlbauer, WolfgangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Okamoto, NobuhikoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Varghese, VinodUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Irving, RachelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sigaudy, SabineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Williams, DeniseUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ahmed, S. FaisalUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bonnard, CarineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kong, Mung KeiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ratbi, IlhamUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fejjal, NawfalUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fikri, MeriemUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Elalaoui, Siham ChafaiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reigstad, HallvardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bole-Feysot, ChristineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nitschke, PatrickUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ragge, NicolaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Levy, NicolasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tuncbilek, GoekhanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Teo, Audrey S. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cunningham, Michael L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sefiani, AbdelazizUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kayserili, HuelyaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Murphy, James M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chatdokmaiprai, ChalermpongUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hillmer, Axel M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wattanasirichaigoon, DuangrurdeeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lyonnet, StanislasUNSPECIFIEDorcid.org/0000-0001-5426-9417UNSPECIFIED
Magdinier, FrederiqueUNSPECIFIEDorcid.org/0000-0002-0159-9559UNSPECIFIED
Javed, AsifUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Blewitt, Marnie E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Amiel, JeanneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wollnik, BerndUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reversade, BrunoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-241857
DOI: 10.1038/ng.3765
Journal or Publication Title: Nature Genet.
Volume: 49
Number: 2
Page Range: S. 249 - 256
Date: 2017
Publisher: NATURE PUBLISHING GROUP
Place of Publication: NEW YORK
ISSN: 1546-1718
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
INACTIVE X-CHROMOSOME; STRUCTURAL-MAINTENANCE; HINGE DOMAIN; METHYLATION; REPAIR; GHKLMultiple languages
Genetics & HeredityMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/24185

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