TY - JOUR
T1 - Carriers and patients with muscle-eye-brain disease can be rapidly diagnosed by enzymatic analysis of fibroblasts and lymphoblasts
AU - Vajsar, Jiri
AU - Zhang, Wenli
AU - Dobyns, William B.
AU - Biggar, Doug
AU - Holden, Kenton R.
AU - Hawkins, Cynthia
AU - Ray, Peter
AU - Olney, Ann H.
AU - Burson, Catherine M.
AU - Srivastava, Anand K.
AU - Schachter, Harry
N1 - 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).
PY - 2006/2
Y1 - 2006/2
N2 - 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.
AB - 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.
KW - Congenital muscular dystrophy
KW - Muscle-eye-brain disease
KW - POMGnT1
UR - http://www.scopus.com/inward/record.url?scp=31944435512&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=31944435512&partnerID=8YFLogxK
U2 - 10.1016/j.nmd.2005.11.012
DO - 10.1016/j.nmd.2005.11.012
M3 - Article
C2 - 16427280
AN - SCOPUS:31944435512
SN - 0960-8966
VL - 16
SP - 132
EP - 136
JO - Neuromuscular Disorders
JF - Neuromuscular Disorders
IS - 2
ER -