Balasubramanian Karthika, Li Bing, Krakow Deborah, Nevarez Lisette, Ho Patric J, Ainsworth Julia A, Nickerson Deborah A, Bamshad Michael J, Immken LaDonna, Lachman Ralph S, Cohn Daniel H
Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, California.
Department of Orthopaedic Surgery, University of California Los Angeles, Los Angeles, California.
Am J Med Genet A. 2017 Sep;173(9):2415-2421. doi: 10.1002/ajmg.a.38349. Epub 2017 Jul 25.
Multiple Epiphyseal Dysplasia (MED) is a relatively mild skeletal dysplasia characterized by mild short stature, joint pain, and early-onset osteoarthropathy. Dominantly inherited mutations in COMP, MATN3, COL9A1, COL9A2, and COL9A3, and recessively inherited mutations in SLC26A2, account for the molecular basis of disease in about 80-85% of the cases. In two families with recurrent MED of an unknown molecular basis, we used exome sequencing and candidate gene analysis to identify homozygosity for recessively inherited missense mutations in CANT1, which encodes calcium-activated nucleotidase 1. The MED phenotype is thus allelic to the more severe Desbuquois dysplasia phenotype and the results identify CANT1 as a second locus for recessively inherited MED.
多发性骨骺发育不良（MED）是一种相对较轻的骨骼发育不良，其特征为身材轻度矮小、关节疼痛和早发性骨关节炎。COMP、MATN3、COL9A1、COL9A2和COL9A3中的显性遗传突变，以及SLC26A2中的隐性遗传突变，约占80 - 85%病例的疾病分子基础。在两个分子基础不明的复发性MED家族中，我们使用外显子组测序和候选基因分析，确定了编码钙激活核苷酸酶1的CANT1中隐性遗传错义突变的纯合性。因此，MED表型与更严重的德布凯发育异常表型等位，结果确定CANT1为隐性遗传MED的第二个基因座。
