MED resulting from recessively inherited mutations in the gene encoding calcium-activated nucleotidase CANT1

  • Am J Med Genet A. 2017 Sep;173(9):2415-2421. doi: 10.1002/ajmg.a.38349.
Karthika Balasubramanian  1 ,  Bing Li  1 ,  Deborah Krakow  2  3  4 ,  Lisette Nevarez  1 ,  Patric J Ho  1 ,  Julia A Ainsworth  1 ,  Deborah A Nickerson  5 ,  Michael J Bamshad  5  6 ,  LaDonna Immken  7 ,  Ralph S Lachman  4 ,  Daniel H Cohn  1  2  4
Affiliations
  • 1. Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, California.
  • 2. Department of Orthopaedic Surgery, University of California Los Angeles, Los Angeles, California.
  • 3. Department of Human Genetics, University of California Los Angeles, Los Angeles, California.
  • 4. International Skeletal Dysplasia Registry, University of California Los Angeles, Los Angeles, California.
  • 5. Department of Genome Sciences, University of Washington, Seattle, Washington.
  • 6. Department of Pediatrics, University of Washington, Seattle, Washington.
  • 7. Specially For Children Genetics, Austin, Texas.
PMID: 28742282 DOI: 10.1002/ajmg.a.38349
Abstract

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.

Keywords
CANT1; chondrodysplasia; desbuquois dysplasia; multiple epiphyseal dysplasia; skeletal dysplasia.