2. Academic Validation
  3. Expanding the molecular and clinical phenotypes of FUT8-CDG

Expanding the molecular and clinical phenotypes of FUT8-CDG

  • J Inherit Metab Dis. 2020 Jul;43(4):871-879. doi: 10.1002/jimd.12221.
Bobby G Ng 1,  Hassan Dastsooz 2 3,  Mohammad Silawi 3,  Parham Habibzadeh 3,  Shima B Jahan 3,  Mohammad A F Fard 3,  Benjamin J Halliday 4,  Kimiyo Raymond 5,  Maura R Z Ruzhnikov 6 7,  Zahra Tabatabaei 3,  Afsaneh Taghipour-Sheshdeh 3,  Elise Brimble 6,  Stephen P Robertson 4,  Mohammad A Faghihi 3 8,  Hudson H Freeze 1
Affiliations

Affiliations

  • 1 Human Genetics Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California.
  • 2 Department of Life Sciences and Systems Biology, Italian Institute for Genomic Medicine (IIGM), University of Turin, Turin, Italy.
  • 3 Persian BayanGene Research and Training Center, Shiraz University of Medical Sciences, Shiraz, Iran.
  • 4 Department of Women's and Children's Health, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
  • 5 Biochemical Genetics Laboratory, Mayo Clinic College of Medicine, Rochester, Minnesota.
  • 6 Department of Neurology and Neurological Sciences, Stanford Medicine, Stanford, California.
  • 7 Division of Medical Genetics, Department of Pediatrics, Stanford Medicine, Stanford, California.
  • 8 Center for Therapeutic Innovation, Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, Florida.
PMID: 32049367 DOI: 10.1002/jimd.12221
Abstract

Pathogenic variants in the Golgi localised alpha 1,6 fucosyltransferase, FUT8, cause a rare inherited metabolic disorder known as FUT8-CDG. To date, only three affected individuals have been reported presenting with a constellation of symptoms including intrauterine growth restriction, severe delays in growth and development, other neurological impairments, significantly shortened limbs, respiratory complications, and shortened lifespan. Here, we report an additional four unrelated affected individuals homozygous for novel pathogenic variants in FUT8. Analysis of serum N-glycans revealed a complete lack of core fucosylation, an important diagnostic biomarker of FUT8-CDG. Our data expands both the molecular and clinical phenotypes of FUT8-CDG and highlights the importance of identifying a reliable biomarker for confirming potentially pathogenic variants.

Keywords

N-glycans; congenital disorders of glycosylation; core fucosylation; mass spectrometry; whole exome sequencing.

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