TY - JOUR
T1 - Heterozygous UDP-GlcNAc 2-epimerase and N-acetylmannosamine kinase domain mutations in the GNE gene result in a less severe GNE myopathy phenotype compared to homozygous N-acetylmannosamine kinase domain mutations
AU - Mori-Yoshimura, Madoka
AU - Monma, Kazunari
AU - Suzuki, Naoki
AU - Aoki, Masashi
AU - Kumamoto, Toshihide
AU - Tanaka, Keiko
AU - Tomimitsu, Hiroyuki
AU - Nakano, Satoshi
AU - Sonoo, Masahiro
AU - Shimizu, Jun
AU - Sugie, Kazuma
AU - Nakamura, Harumasa
AU - Oya, Yasushi
AU - Hayashi, Yukiko K.
AU - Malicdan, May Christine V.
AU - Noguchi, Satoru
AU - Murata, Miho
AU - Nishino, Ichizo
N1 - Funding Information:
We thank members of the Patients Association for Distal Myopathies (PADM) for their help. This work was partly supported by the Research on Intractable Diseases of Health and Labor Sciences Research Grants ; Comprehensive Research on Disability Health and Welfare Grants , Health and Labor Science Research Grants ; Intramural Research Grant ( 23-4 , 23-5 ) for Neurological and Psychiatric Disorders of NCNP; and a Young Investigator Fellowship from the Translational Medical Center, NCNP.
Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2012/7/15
Y1 - 2012/7/15
N2 - Background: Glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase (GNE) myopathy, also called distal myopathy with rimmed vacuoles (DMRV) or hereditary inclusion body myopathy (HIBM), is a rare, progressive autosomal recessive disorder caused by mutations in the GNE gene. Here, we examined the relationship between genotype and clinical phenotype in participants with GNE myopathy. Methods: Participants with GNE myopathy were asked to complete a questionnaire regarding medical history and current symptoms. Results: A total of 71 participants with genetically confirmed GNE myopathy (27 males and 44 females; mean age, 43.1 ± 13.0 (mean ± SD) years) completed the questionnaire. Initial symptoms (e.g., foot drop and lower limb weakness) appeared at a mean age of 24.8 ± 8.3 years. Among the 71 participants, 11 (15.5%) had the ability to walk, with a median time to loss of ambulation of 17.0 ± 2.1 years after disease onset. Participants with a homozygous mutation (p.V572L) in the N-acetylmannosamine kinase domain (KD/KD participants) had an earlier disease onset compared to compound heterozygous participants with mutations in the uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) 2-epimerase and N-acetylmannosamine kinase domains (ED/KD participants; 26.3 ± 7.3 vs. 21.2 ± 11.1 years, respectively). KD/KD participants were more frequently non-ambulatory compared to ED/KD participants at the time of survey (80% vs. 50%). Data were verified using medical records available from 17 outpatient participants. Conclusions: Homozygous KD/KD participants exhibited a more severe phenotype compared to heterozygous ED/KD participants.
AB - Background: Glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase (GNE) myopathy, also called distal myopathy with rimmed vacuoles (DMRV) or hereditary inclusion body myopathy (HIBM), is a rare, progressive autosomal recessive disorder caused by mutations in the GNE gene. Here, we examined the relationship between genotype and clinical phenotype in participants with GNE myopathy. Methods: Participants with GNE myopathy were asked to complete a questionnaire regarding medical history and current symptoms. Results: A total of 71 participants with genetically confirmed GNE myopathy (27 males and 44 females; mean age, 43.1 ± 13.0 (mean ± SD) years) completed the questionnaire. Initial symptoms (e.g., foot drop and lower limb weakness) appeared at a mean age of 24.8 ± 8.3 years. Among the 71 participants, 11 (15.5%) had the ability to walk, with a median time to loss of ambulation of 17.0 ± 2.1 years after disease onset. Participants with a homozygous mutation (p.V572L) in the N-acetylmannosamine kinase domain (KD/KD participants) had an earlier disease onset compared to compound heterozygous participants with mutations in the uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) 2-epimerase and N-acetylmannosamine kinase domains (ED/KD participants; 26.3 ± 7.3 vs. 21.2 ± 11.1 years, respectively). KD/KD participants were more frequently non-ambulatory compared to ED/KD participants at the time of survey (80% vs. 50%). Data were verified using medical records available from 17 outpatient participants. Conclusions: Homozygous KD/KD participants exhibited a more severe phenotype compared to heterozygous ED/KD participants.
KW - (UDP-N-acetyl)-2-epimerase domain
KW - Distal myopathy with rimmed vacuoles
KW - GNE myopathy
KW - Glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase
KW - Hereditary inclusion body myopathy
KW - N-acetylmannosamine kinase domain
KW - Natural history
KW - Questionnaire
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U2 - 10.1016/j.jns.2012.03.016
DO - 10.1016/j.jns.2012.03.016
M3 - Article
C2 - 22507750
AN - SCOPUS:84861639380
VL - 318
SP - 100
EP - 105
JO - Journal of the Neurological Sciences
JF - Journal of the Neurological Sciences
SN - 0022-510X
IS - 1-2
ER -