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.

Authors:
Ichizo Nishino, MD, PhD
Ichizo Nishino, MD, PhD
National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP)
Director, Department of Neuromuscular Research
Muscle disease
Kodaira, Tokyo | Japan

J Neurol Sci 2012 Jul 14;318(1-2):100-5. Epub 2012 Apr 14.

Department of Neurology, National Center Hospital, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8551, Japan.

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.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jns.2012.03.016DOI Listing
July 2012
68 Reads
14 Citations
2.474 Impact Factor

Publication Analysis

Top Keywords

n-acetylmannosamine kinase
16
gne myopathy
16
kd/kd participants
12
kinase domain
12
participants
12
ed/kd participants
12
gne gene
8
disease onset
8
2-epimerase n-acetylmannosamine
8
mutations gne
8
domain mutations
8
phenotype compared
8
udp-glcnac 2-epimerase
8
participants gne
8
gne
7
myopathy
6
kinase
5
age 431±130
4
263±73 212±111
4
212±111 years
4

Similar Publications