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CSGALNACT1-congenital disorder of glycosylation: A mild skeletal dysplasia with advanced bone age.

Publication ,  Journal Article
Mizumoto, S; Janecke, AR; Sadeghpour, A; Povysil, G; McDonald, MT; Unger, S; Greber-Platzer, S; Deak, KL; Katsanis, N; Superti-Furga, A ...
Published in: Hum Mutat
March 2020

Congenital disorders of glycosylation (CDGs) comprise a large number of inherited metabolic defects that affect the biosynthesis and attachment of glycans. CDGs manifest as a broad spectrum of disease, most often including neurodevelopmental and skeletal abnormalities and skin laxity. Two patients with biallelic CSGALNACT1 variants and a mild skeletal dysplasia have been described previously. We investigated two unrelated patients presenting with short stature with advanced bone age, facial dysmorphism, and mild language delay, in whom trio-exome sequencing identified novel biallelic CSGALNACT1 variants: compound heterozygosity for c.1294G>T (p.Asp432Tyr) and the deletion of exon 4 that includes the start codon in one patient, and homozygosity for c.791A>G (p.Asn264Ser) in the other patient. CSGALNACT1 encodes CSGalNAcT-1, a key enzyme in the biosynthesis of sulfated glycosaminoglycans chondroitin and dermatan sulfate. Biochemical studies demonstrated significantly reduced CSGalNAcT-1 activity of the novel missense variants, as reported previously for the p.Pro384Arg variant. Altered levels of chondroitin, dermatan, and heparan sulfate moieties were observed in patients' fibroblasts compared to controls. Our data indicate that biallelic loss-of-function mutations in CSGALNACT1 disturb glycosaminoglycan synthesis and cause a mild skeletal dysplasia with advanced bone age, CSGALNACT1-CDG.

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Published In

Hum Mutat

DOI

EISSN

1098-1004

Publication Date

March 2020

Volume

41

Issue

3

Start / End Page

655 / 667

Location

United States

Related Subject Headings

  • Phenotype
  • Pedigree
  • N-Acetylgalactosaminyltransferases
  • Mutation, Missense
  • Mutation
  • Musculoskeletal Abnormalities
  • Male
  • Loss of Function Mutation
  • Infant, Newborn
  • Humans
 

Citation

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Mizumoto, S., Janecke, A. R., Sadeghpour, A., Povysil, G., McDonald, M. T., Unger, S., … Vodopiutz, J. (2020). CSGALNACT1-congenital disorder of glycosylation: A mild skeletal dysplasia with advanced bone age. Hum Mutat, 41(3), 655–667. https://doi.org/10.1002/humu.23952
Mizumoto, Shuji, Andreas R. Janecke, Azita Sadeghpour, Gundula Povysil, Marie T. McDonald, Sheila Unger, Susanne Greber-Platzer, et al. “CSGALNACT1-congenital disorder of glycosylation: A mild skeletal dysplasia with advanced bone age.Hum Mutat 41, no. 3 (March 2020): 655–67. https://doi.org/10.1002/humu.23952.
Mizumoto S, Janecke AR, Sadeghpour A, Povysil G, McDonald MT, Unger S, et al. CSGALNACT1-congenital disorder of glycosylation: A mild skeletal dysplasia with advanced bone age. Hum Mutat. 2020 Mar;41(3):655–67.
Mizumoto, Shuji, et al. “CSGALNACT1-congenital disorder of glycosylation: A mild skeletal dysplasia with advanced bone age.Hum Mutat, vol. 41, no. 3, Mar. 2020, pp. 655–67. Pubmed, doi:10.1002/humu.23952.
Mizumoto S, Janecke AR, Sadeghpour A, Povysil G, McDonald MT, Unger S, Greber-Platzer S, Deak KL, Katsanis N, Superti-Furga A, Sugahara K, Davis EE, Yamada S, Vodopiutz J. CSGALNACT1-congenital disorder of glycosylation: A mild skeletal dysplasia with advanced bone age. Hum Mutat. 2020 Mar;41(3):655–667.
Journal cover image

Published In

Hum Mutat

DOI

EISSN

1098-1004

Publication Date

March 2020

Volume

41

Issue

3

Start / End Page

655 / 667

Location

United States

Related Subject Headings

  • Phenotype
  • Pedigree
  • N-Acetylgalactosaminyltransferases
  • Mutation, Missense
  • Mutation
  • Musculoskeletal Abnormalities
  • Male
  • Loss of Function Mutation
  • Infant, Newborn
  • Humans