
Inherited CHST11/MIR3922 deletion is associated with a novel recessive syndrome presenting with skeletal malformation and malignant lymphoproliferative disease
Author(s) -
Chopra Sameer S.,
Leshchiner Ignaty,
Duzkale Hatice,
McLaughlin Heather,
Giovanni Monica,
Zhang Chengsheng,
Stitziel Nathan,
Fingeroth Joyce,
Joyce Robin M.,
Lebo Matthew,
Rehm Heidi,
Vuzman Dana,
Maas Richard,
Sunyaev Shamil R.,
Murray Michael,
Cassa Christopher A.
Publication year - 2015
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.152
Subject(s) - proband , biology , mucopolysaccharidosis , genetics , mutation , gene , biochemistry
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.