Two families with spondylo-epi-metaphyseal dysplasia due to compound heterozygocity in the vWFA domain of MATN3

Eur J Med Genet. 2024 Dec:72:104972. doi: 10.1016/j.ejmg.2024.104972. Epub 2024 Sep 16.

Abstract

Heterozygous variants of MATN3 is one of the common causes of multiple epiphyseal dysplasia (MED). Here we report three individuals from two unrelated families who harbor compound heterozygous variants in MATN3 (p.Arg121Trp and p.Val220Ala). Contrary to the MED phenotype, these individuals exhibit spondyloepimetaphyseal dysplasia (SEMD) resembling the phenotypes caused by homozygous MATN3 variants. Clinical manifestations included short stature, aggravating genu varum, joint laxity, and spinal abnormalities. Radiographic findings were distinct from typical MED. These compound heterozygous variants in the von Willebrand factor A domain of MATN3 expand the phenotypic spectrum associated with MATN3, and suggest that extreme MATN3 dysfunction resulting from dual variants can lead to a specific pattern of SEMD.

Keywords: Compound heterozygous; MATN3; Multiple epiphyseal dysplasia; Spondyloepipmetaphyseal dysplasia.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Female
  • Heterozygote*
  • Humans
  • Male
  • Matrilin Proteins
  • Mutation
  • Osteochondrodysplasias* / genetics
  • Osteochondrodysplasias* / pathology
  • Pedigree*
  • Phenotype*
  • Protein Domains

Substances

  • MATN3 protein, human
  • Matrilin Proteins