Carriers and patients with muscle-eye-brain disease can be rapidly diagnosed by enzymatic analysis of fibroblasts and lymphoblasts

Jiri Vajsar, Wenli Zhang, William B. Dobyns, Doug Biggar, Kenton R. Holden, Cynthia Hawkins, Peter Ray, Ann H. Olney, Catherine M. Burson, Anand K. Srivastava, Harry Schachter

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

We report a new fibroblast and lymphoblast based protein O-mannosyl β-1,2-N-acetylglucosaminyltransferase 1 enzymatic assay, which allows rapid and accurate diagnosis of carriers and patients with muscle-eye-brain type of congenital muscular dystrophy. Seven patients with genetically confirmed muscle-eye-brain disease were assayed for protein O-mannosyl β-1,2-N-acetylglucosaminyltransferase 1 enzyme activity. In three patients and their heterozygous parents, the assays were done on EBV-transformed lymphoblasts, in another three patients they were done on cultured fibroblasts and in the last patient on both fibroblasts and lymphoblasts. Cultured fibroblasts and lymphoblasts from the muscle-eye-brain patients showed a highly significant decrease in protein O-mannosyl β-1,2-N- acetylglucosaminyltransferase 1 activity relative to controls. The residual protein O-mannosyl β-1,2-N-acetylglucosaminyltransferase 1 level in fibroblasts (average 0.11 nmoles/h per mg) was about 13% of normal controls. The ratio of protein O-mannosyl β-1,2-N-acetylglucosaminyltransferase 1 activity to the activity of a glycosyltransferase control (N- acetylglucosaminyltransferase 1; GnT1) in fibroblasts was on average 0.006 in muscle-eye-brain patients and 0.045 in controls. The average residual protein O-mannosyl β-1,2-N-acetylglucosaminyltransferase 1 level in lymphoblasts was 15% of normal controls. The average ratio of protein O-mannosyl β-1,2-N-acetylglucosaminyltransferase 1/GnT1 activity was 0.007 in muscle-eye-brain patients, 0.026 in heterozygous carriers and 0.046 in normal controls. Assay of protein O-mannosyl β-1,2-N-acetylglucosaminyltransferase 1 activity in fibroblasts and lymphoblasts from muscle-eye-brain carriers and patients provides a rapid and relatively simple diagnostic test for this disease and could be used as a screening test in carriers and patients with complex congenital muscular dystrophy.

Original languageEnglish (US)
Pages (from-to)132-136
Number of pages5
JournalNeuromuscular Disorders
Volume16
Issue number2
DOIs
StatePublished - Feb 2006
Externally publishedYes

Bibliographical note

Funding Information:
This study was supported by a grant from the Physicians' Services Incorporated Foundation and in part by a grant from the South Carolina Department of Disabilities and Special Needs (SCDDSN).

Keywords

  • Congenital muscular dystrophy
  • Muscle-eye-brain disease
  • POMGnT1

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