Journal article
Mutations in SEC24D, encoding a component of the COPII machinery, cause a syndromic form of osteogenesis imperfecta
L Garbes, K Kim, A Rieß, H Hoyer-Kuhn, F Beleggia, A Bevot, MJ Kim, YH Huh, HS Kweon, R Savarirayan, D Amor, PM Kakadia, T Lindig, KO Kagan, J Becker, SA Boyadjiev, B Wollnik, O Semler, SK Bohlander, J Kim Show all
American Journal of Human Genetics | Published : 2015
Abstract
As a result of a whole-exome sequencing study, we report three mutant alleles in SEC24D, a gene encoding a component of the COPII complex involved in protein export from the ER: the truncating mutation c.613C>T (p.Gln205∗) and the missense mutations c.3044C>T (p.Ser1015Phe, located in a cargo-binding pocket) and c.2933A>C (p.Gln978Pro, located in the gelsolin-like domain). Three individuals from two families affected by a similar skeletal phenotype were each compound heterozygous for two of these mutant alleles, with c.3044C>T being embedded in a 14 Mb founder haplotype shared by all three. The affected individuals were a 7-year-old boy with a phenotype most closely resembling Cole-Carpenter..
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Awarded by National Institutes of Health
Funding Acknowledgements
We are grateful to all family members that participated in this study and to Saskia Seland for excellent technical assistance. We would like to thank Philipp Greif and Nikola Konstandin (Department of Medicine III, University of Munich) as well as Stefan Krebs, Alexander Graf, and Helmut Blum (LaFuGA, Gene Center, University of Munich) for support in exome sequencing. The authors would like to thank the Exome Aggregation Consortium and the groups that provided exome variant data for comparison. A full list of groups contributing to ExAC can be found online. The authors would also like to thank the NHLBI GO Exome Sequencing Project and its ongoing studies, which produced and provided exome variant calls for comparison: the Lung GO Sequencing Project (HL-102923), the WHI Sequencing Project (HL-102924), the Broad GO Sequencing Project (HL-102925), the Seattle GO Sequencing Project (HL-102926), and the Heart GO Sequencing Project (HL-103010). This work was supported in part by grants to J.K. from the National Institute of Dental and Craniofacial Research/NIH (R21 DE022419) and the National Institute of General Medical Sciences/NIH (R01 GM110373), by grants to B.W. from the German Federal Ministry of Education and Research (BMBF), grant number 01GM1211A (E-RARE network CRANIRARE-2), and grant number 01GM1109C (national rare disease network FACE), and by grants to H.-S.K. from Korea Basic Science Institute (E34700) and the Bio & Medical Technology Development Program of the National Research Foundation funded by the Ministry of Science, ICT & Future Planning (2013M3A9A9050076).