2. Academic Validation
  3. Biallelic CSGALNACT1-mutations cause a mild skeletal dysplasia

Biallelic CSGALNACT1-mutations cause a mild skeletal dysplasia

  • Bone. 2019 Oct;127:446-451. doi: 10.1016/j.bone.2019.07.016.
R Meyer 1,  S Schacht 2,  L Buschmann 1,  M Begemann 1,  F Kraft 1,  N Haag 1,  A Kochs 3,  A Schulze 4,  I Kurth 1,  M Elbracht 5
Affiliations

Affiliations

  • 1 Institute of Human Genetics, Medical Faculty, RWTH Aachen University, Aachen, Germany.
  • 2 Department for Radiology, Medical Faculty, RWTH Aachen University, Aachen, Germany.
  • 3 Gemeinschaftspraxis Dr. Kochs/Dr. Rode, Aachen, Germany.
  • 4 Department for Orthopedics, Medical Faculty, RWTH Aachen University, Aachen, Germany.
  • 5 Institute of Human Genetics, Medical Faculty, RWTH Aachen University, Aachen, Germany. Electronic address: [email protected].
PMID: 31325655 DOI: 10.1016/j.bone.2019.07.016
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.

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