Biallelic CSGALNACT1-mutations cause a mild skeletal dysplasia
- Bone. 2019 Oct;127:446-451. doi: 10.1016/j.bone.2019.07.016.
- 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].
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.