A second individual with rhizomelic spondyloepimetaphyseal dysplasia and homozygous variant in GNPNAT1

Eur J Med Genet. 2022 Jun;65(6):104495. doi: 10.1016/j.ejmg.2022.104495. Epub 2022 Apr 12.


Spondyloepimetaphyseal dysplasias (SEMDs) belong to a clinically and genetically heterogeneous group of inherited skeletal disorders defined by a defect in the growth and shape of vertebrae, epiphyses and metaphyses. Rhizomelic SEMD is characterized by a disproportionate small stature caused by severe shortening and deformation of the limbs' proximal bones, with the cranio-facial sphere unaffected. We report a second individual, an 8-year-old girl, with autosomal recessive rhizomelic SEMD associated with a homozygous exonic missense variant, c.226G > A p.(Glu76Lys), in GNPNAT1 identified by trio genome sequencing. Our data corroborate the recent findings of Ain et al. and further delineate the clinical and radiographic features of this form of SEMD associated with rhizomelic dysplasia while outlining a potential hotspot in this newly described genetic disorder.

Keywords: GNPNAT1; Heparan sulfate; Skeletal disorder; Spondyloepimetaphyseal dysplasia.

Publication types

  • Case Reports

MeSH terms

  • Bone and Bones
  • Child
  • Dwarfism* / diagnostic imaging
  • Dwarfism* / genetics
  • Female
  • Glucosamine 6-Phosphate N-Acetyltransferase / genetics
  • Homozygote
  • Humans
  • Mutation, Missense
  • Osteochondrodysplasias* / diagnostic imaging
  • Osteochondrodysplasias* / genetics
  • Rare Diseases


  • GNPNAT1 protein, human
  • Glucosamine 6-Phosphate N-Acetyltransferase