PMID- 27829678
OWN - NLM
STAT- MEDLINE
DCOM- 20170524
LR  - 20181113
IS  - 1435-232X (Electronic)
IS  - 1434-5161 (Linking)
VI  - 62
IP  - 2
DP  - 2017 Feb
TI  - Missing genetic variations in GNE myopathy: rearrangement hotspots encompassing 
      5'UTR and founder allele.
PG  - 159-166
LID - 10.1038/jhg.2016.134 [doi]
AB  - GNE myopathy is an autosomal recessive distal myopathy caused by loss-of-function 
      mutations in the GNE gene, which encodes UDP-GlcNAc 2-epimerase/ManNAc kinase 
      (GNE), a key enzyme in sialic-acid biosynthesis. By comprehensive screening of 
      manifesting patients using a fine-mapped targeted next-generation sequencing 
      (NGS), we identified copy number variations (CNVs) in 13 patients from 11 
      unrelated families. The nine unique CNVs largely vary in size from 0.3 to 72 kb. 
      Over half of the cases carry different deletions spanning merely exon 2, which 
      contains the 5' untranslated region (5'UTR) of the muscle major transcript hGNE1. 
      Of most unique CNVs, either the telomeric or the centromeric breakpoint locates 
      within intron 2, indicating rearrangement hotspots. Haplotype analysis suggested 
      the existence of a founder allele with exon 2 deletion. The breakpoints for all 
      CNVs were determined by long-range PCR and sequencing. All of the breakpoints of 
      gross deletion/duplications reside within directly oriented pairs of Alu repeats. 
      The results of this study firstly widen the spectra of mutations to CNVs 
      encompassing 5'UTR, underscoring the pivotal role of the hGNE1 transcript. 
      Alu-mediated non-recurrent CNVs may have been overlooked in a wide variety of 
      recessive phenotypes, especially in those associated with genomic Alu-rich genes 
      such as GNE.
FAU - Zhu, Wenhua
AU  - Zhu W
AD  - Department of Neuromuscular Research, National Institute of Neuroscience, Tokyo, 
      Japan.
AD  - Department of Genome Medicine Development, Medical Genome Center (MGC), National 
      Center of Neurology and Psychiatry, Tokyo, Japan.
AD  - Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China.
FAU - Mitsuhashi, Satomi
AU  - Mitsuhashi S
AD  - Department of Neuromuscular Research, National Institute of Neuroscience, Tokyo, 
      Japan.
AD  - Department of Genome Medicine Development, Medical Genome Center (MGC), National 
      Center of Neurology and Psychiatry, Tokyo, Japan.
FAU - Yonekawa, Takahiro
AU  - Yonekawa T
AD  - Department of Neuromuscular Research, National Institute of Neuroscience, Tokyo, 
      Japan.
FAU - Noguchi, Satoru
AU  - Noguchi S
AD  - Department of Neuromuscular Research, National Institute of Neuroscience, Tokyo, 
      Japan.
AD  - Department of Genome Medicine Development, Medical Genome Center (MGC), National 
      Center of Neurology and Psychiatry, Tokyo, Japan.
FAU - Huei, Josiah Chai Yui
AU  - Huei JC
AD  - Department of Neurology, National Neuroscience Institute, Singapore, Singapore.
FAU - Nalini, Atchayaram
AU  - Nalini A
AD  - Department of Neurology, Bangalore, India.
FAU - Preethish-Kumar, Veeramani
AU  - Preethish-Kumar V
AD  - Department of Clinical Neurosciences, National Institute of Mental Health and 
      Neurosciences, Bangalore, India.
FAU - Yamamoto, Masayoshi
AU  - Yamamoto M
AD  - Department of Neurology, Kansai Electric Power Hospital, Osaka, Japan.
FAU - Murakata, Kenji
AU  - Murakata K
AD  - Department of Neurology, Kansai Electric Power Hospital, Osaka, Japan.
FAU - Mori-Yoshimura, Madoka
AU  - Mori-Yoshimura M
AD  - Department of Neurology, National Center Hospital, National Center of Neurology 
      and Psychiatry, Tokyo, Japan.
FAU - Kamada, Sachiko
AU  - Kamada S
AD  - Department of Neurology, Akita University Graduate School of Medicine, Akita, 
      Japan.
FAU - Yahikozawa, Hiroyuki
AU  - Yahikozawa H
AD  - Department of Neurology, Nagano Red Cross Hospital, Nagano, Japan.
FAU - Karasawa, Masato
AU  - Karasawa M
AD  - Shizusato Shinryojo, Gifu, Japan.
FAU - Kimura, Seigo
AU  - Kimura S
AD  - Department of Neurology, Graduate School of Medicine, Nagoya University, Nagoya, 
      Japan.
FAU - Yamashita, Fumitada
AU  - Yamashita F
AD  - Department of Neurology, Ogaki Municipal Hospital, Gifu, Japan.
FAU - Nishino, Ichizo
AU  - Nishino I
AD  - Department of Neuromuscular Research, National Institute of Neuroscience, Tokyo, 
      Japan.
AD  - Department of Genome Medicine Development, Medical Genome Center (MGC), National 
      Center of Neurology and Psychiatry, Tokyo, Japan.
LA  - eng
PT  - Journal Article
DEP - 20161110
PL  - England
TA  - J Hum Genet
JT  - Journal of human genetics
JID - 9808008
RN  - 0 (5' Untranslated Regions)
RN  - 0 (Multienzyme Complexes)
RN  - 0 (UDP-N-acetylglucosamine 2-epimerase - N-acetylmannosamine kinase)
RN  - Distal myopathy, Nonaka type
SB  - IM
MH  - 5' Untranslated Regions/*genetics
MH  - Adult
MH  - Base Sequence
MH  - DNA Copy Number Variations/*genetics
MH  - Distal Myopathies/*genetics
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - Genetic Testing
MH  - Genome/genetics
MH  - Genome-Wide Association Study
MH  - Haplotypes/genetics
MH  - Humans
MH  - Male
MH  - Multienzyme Complexes/*genetics
MH  - Mutation, Missense/genetics
MH  - Polymerase Chain Reaction
MH  - Sequence Analysis, DNA
MH  - Sequence Deletion/genetics
MH  - Young Adult
EDAT- 2016/11/11 06:00
MHDA- 2017/05/26 06:00
CRDT- 2016/11/11 06:00
PHST- 2016/07/24 00:00 [received]
PHST- 2016/09/17 00:00 [revised]
PHST- 2016/09/30 00:00 [accepted]
PHST- 2016/11/11 06:00 [pubmed]
PHST- 2017/05/26 06:00 [medline]
PHST- 2016/11/11 06:00 [entrez]
AID - jhg2016134 [pii]
AID - 10.1038/jhg.2016.134 [doi]
PST - ppublish
SO  - J Hum Genet. 2017 Feb;62(2):159-166. doi: 10.1038/jhg.2016.134. Epub 2016 Nov 10.