Deactivating Germline Mutations in LEMD3 Cause Osteopoikilosis and Buschke-Ollendorff Syndrome, but Not Sporadic Melorheostosis

作者：Steven Mumm, Deborah Wenkert, Xiafang Zhang, William H. McAlister, Richard J. Mier, Michael P. Whyte · 发表于：Journal of Bone and Mineral Research · 年份：2006 · DOI：10.1359/jbmr.061102 · 被引用次数：85 · 研究领域：Dermatological and Skeletal Disorders、Heterotopic Ossification and Related Conditions、Parathyroid Disorders and Treatments

UNLABELLED: Autosomal dominant OPK and BOS feature widespread foci of osteosclerotic trabeculae without or with skin lesions, respectively. Occasionally, a larger area of dense bone in OPK or BOS resembles MEL, a sporadic sclerosing disorder primarily involving cortical bone. Others, finding deactivating germline LEMD3 mutations in OPK or BOS, concluded such defects explain all three conditions. We found germline LEMD3 mutations in OPK and BOS but not in sporadic MEL. INTRODUCTION: In 2004, others discovered that heterozygous, loss-of-function, germline mutations in the LEMD3 gene (LEMD3 or MAN1) cause both osteopoikilosis (OPK) and Buschke-Ollendorff syndrome (BOS). OPK is an autosomal dominant, usually benign, skeletal dysplasia featuring multiple, small, especially metaphyseal, oval or round, dense trabecular foci distributed symmetrically throughout the skeleton. BOS combines OPK with connective tissue nevi comprised of collagen and elastin. In some OPK and BOS families, an individual may have relatively large, asymmetric areas of dense cortical bone interpreted as melorheostosis (MEL). MEL, however, classically refers to a sporadic, troublesome skeletal dysostosis featuring large, asymmetric, "flowing hyperostosis" of long bone cortices often with overlying, constricting soft tissue abnormalities. However, a heterozygous germline mutation in LEMD3 was offered to explain MEL. MATERIALS AND METHODS: We studied 11 unrelated individuals with sclerosing bone disorders where L...