Biallelic CSGALNACT1-mutations cause a mild skeletal dysplasia

Bone. 2019 Oct:127:446-451. doi: 10.1016/j.bone.2019.07.016. Epub 2019 Jul 17.

Abstract

Genetic causes of skeletal disorders are manifold and affect, among others, enzymes of bone and connective tissue synthesis pathways. We present a twelve-year-old boy with a mild skeletal dysplasia, hypermobility of joints and axial malalignment of lower limbs and feet. Exome sequencing revealed a biallelic loss of function mutation in CSGALNACT1, which encodes chondroitin sulfate N-acetylgalactosaminyltransferase 1 and plays a major role in the chondroitin sulfate chain biosynthesis and therefore in the synthesis of glycosaminoglycans. Recently, the first case of a pediatric patient with a mild skeletal dysplasia due to a compound heterozygous large intragenic deletion and a damaging missense variant in CSGALNACT1 was reported. We here identify a second case and the first juvenile patient with a homozygous frameshift variant in CSGALNACT1 which corroborates its role in mild and non-progressive skeletal dysplasia with joint laxity.

Keywords: CSGALNACT1; CSGalNAcT-1; Chondroitin sulfate; Skeletal dysplasia.

Publication types

  • Case Reports

MeSH terms

  • Alleles*
  • Body Height
  • Body Weight
  • Child
  • Humans
  • Male
  • Mutation / genetics*
  • N-Acetylgalactosaminyltransferases / genetics*
  • Osteochondrodysplasias / diagnostic imaging
  • Osteochondrodysplasias / enzymology*
  • Osteochondrodysplasias / genetics*

Substances

  • N-Acetylgalactosaminyltransferases
  • chondroitin sulfate N-acetylgalactosaminyltransferase-1