Department of Medicine, Division of Infectious Diseases and Immunology
Genomics | Hemic and Lymphatic Diseases | Molecular Genetics | Musculoskeletal Diseases
Glycosaminoglycans (GAGs) such as chondroitin are ubiquitous disaccharide carbohydrate chains that contribute to the formation and function of proteoglycans at the cell membrane and in the extracellular matrix. Although GAG-modifying enzymes are required for diverse cellular functions, the role of these proteins in human development and disease is less well understood. Here, we describe two sisters out of seven siblings affected by congenital limb malformation and malignant lymphoproliferative disease. Using Whole-Genome Sequencing (WGS), we identified in the proband deletion of a 55 kb region within chromosome 12q23 that encompasses part of CHST11 (encoding chondroitin-4-sulfotransferase 1) and an embedded microRNA (MIR3922). The deletion was homozygous in the proband but not in each of three unaffected siblings. Genotyping data from the 1000 Genomes Project suggest that deletions inclusive of both CHST11 and MIR3922 are rare events. Given that CHST11 deficiency causes severe chondrodysplasia in mice that is similar to human limb malformation, these results underscore the importance of chondroitin modification in normal skeletal development. Our findings also potentially reveal an unexpected role for CHST11 and/or MIR3922 as tumor suppressors whose disruption may contribute to malignant lymphoproliferative disease.
CHST11, inherited lymphoproliferative disorder, malignant lymphoproliferative disorder, MIR3922, skeletal malformation
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Copyright 2015 The Authors. This is an open access article under the term s of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
DOI of Published Version
Mol Genet Genomic Med. 2015 Sep;3(5):413-23. doi: 10.1002/mgg3.152. Epub 2015 May 10. Link to article on publisher's site
Molecular genetics and genomic medicine
Chopra, Sameer S.; Leshchiner, Ignaty; Duzkale, Hatice; McLaughlin, Heather; Giovanni, Monica; Zhang, Chengsheng; Stitziel, Nathan; Fingeroth, Joyce D.; Joyce, Robin M.; Lebo, Matthew; Rehm, Heidi; Vuzman, Dana; Maas, Richard; Sunyaev, Shamil R.; Murray, Michael; and Cassa, Christopher A., "Inherited CHST11/MIR3922 deletion is associated with a novel recessive syndrome presenting with skeletal malformation and malignant lymphoproliferative disease" (2015). Open Access Articles. 2619.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.