PMID- 24521565
OWN - NLM
STAT- MEDLINE
DCOM- 20141002
LR  - 20221207
IS  - 1468-330X (Electronic)
IS  - 0022-3050 (Linking)
VI  - 85
IP  - 9
DP  - 2014 Sep
TI  - Autosomal-recessive complicated spastic paraplegia with a novel lysosomal 
      trafficking regulator gene mutation.
PG  - 1024-8
LID - 10.1136/jnnp-2013-306981 [doi]
AB  - BACKGROUND: Autosomal-recessive hereditary spastic paraplegias (AR-HSP) consist 
      of a genetically diverse group of neurodegenerative diseases characterised by 
      pyramidal tracts dysfunction. The causative genes for many types of AR-HSP remain 
      elusive. We tried to identify the gene mutation for AR-HSP with cerebellar ataxia 
      and neuropathy. METHODS: This study included two patients in a Japanese family 
      with their parents who are first cousins. Neurological examination and gene 
      analysis were conducted in the two patients and two normal family members. We 
      undertook genome-wide linkage analysis employing single nucleotide polymorphism 
      arrays using the two patients' DNAs and exome sequencing using one patient's 
      sample. RESULTS: We detected a homozygous missense mutation (c.4189T>G, p.F1397V) 
      in the lysosomal trafficking regulator (LYST) gene, which is described as the 
      causative gene for Chediak-Higashi syndrome (CHS). CHS is a rare 
      autosomal-recessive syndrome characterised by hypopigmentation, severe immune 
      deficiency, a bleeding tendency and progressive neurological dysfunction. This 
      mutation was co-segregated with the disease in the family and was located at 
      well-conserved amino acid. This LYST mutation was not found in 200 Japanese 
      control DNAs. Microscopic observation of peripheral blood in the two patients 
      disclosed large peroxidase-positive granules in both patients' granulocytes, 
      although they had no symptoms of immune deficiency or bleeding tendency. 
      CONCLUSIONS: We diagnosed these patients as having adult CHS presenting spastic 
      paraplegia with cerebellar ataxia and neuropathy. The clinical spectrum of CHS is 
      broader than previously recognised. Adult CHS must be considered in the 
      differential diagnosis of AR-HSP.
CI  - Published by the BMJ Publishing Group Limited. For permission to use (where not 
      already granted under a licence) please go to 
      http://group.bmj.com/group/rights-licensing/permissions.
FAU - Shimazaki, Haruo
AU  - Shimazaki H
AUID- ORCID: 0000-0003-0628-7164
AD  - Division of Neurology, Department of Internal Medicine, Jichi Medical University 
      School of Medicine, Tochigi, Japan.
FAU - Honda, Junko
AU  - Honda J
AD  - Division of Neurology, Department of Internal Medicine, Jichi Medical University 
      School of Medicine, Tochigi, Japan.
FAU - Naoi, Tametou
AU  - Naoi T
AD  - Division of Neurology, Department of Internal Medicine, Jichi Medical University 
      School of Medicine, Tochigi, Japan.
FAU - Namekawa, Michito
AU  - Namekawa M
AD  - Division of Neurology, Department of Internal Medicine, Jichi Medical University 
      School of Medicine, Tochigi, Japan.
FAU - Nakano, Imaharu
AU  - Nakano I
AD  - Department of Neurology, Tokyo Metropolitan Neurological Hospital, Tokyo, Japan.
FAU - Yazaki, Masahide
AU  - Yazaki M
AD  - Department of Medicine (Neurology and Rheumatology), Shinshu University School of 
      Medicine, Nagano, Japan.
FAU - Nakamura, Katsuya
AU  - Nakamura K
AD  - Department of Medicine (Neurology and Rheumatology), Shinshu University School of 
      Medicine, Nagano, Japan.
FAU - Yoshida, Kunihiro
AU  - Yoshida K
AD  - Department of Medicine (Neurology and Rheumatology), Shinshu University School of 
      Medicine, Nagano, Japan.
FAU - Ikeda, Shu-ichi
AU  - Ikeda S
AD  - Department of Medicine (Neurology and Rheumatology), Shinshu University School of 
      Medicine, Nagano, Japan.
FAU - Ishiura, Hiroyuki
AU  - Ishiura H
AD  - Department of Neurology, Graduate School of Medicine, University of Tokyo, Tokyo, 
      Japan.
FAU - Fukuda, Yoko
AU  - Fukuda Y
AD  - Department of Neurology, Graduate School of Medicine, University of Tokyo, Tokyo, 
      Japan.
FAU - Takahashi, Yuji
AU  - Takahashi Y
AD  - Department of Neurology, Graduate School of Medicine, University of Tokyo, Tokyo, 
      Japan.
FAU - Goto, Jun
AU  - Goto J
AD  - Department of Neurology, Graduate School of Medicine, University of Tokyo, Tokyo, 
      Japan.
FAU - Tsuji, Shoji
AU  - Tsuji S
AD  - Department of Neurology, Graduate School of Medicine, University of Tokyo, Tokyo, 
      Japan.
FAU - Takiyama, Yoshihisa
AU  - Takiyama Y
AD  - Department of Neurology, Interdisciplinary Graduate School of Medicine and 
      Engineering, University of Yamanashi, Yamanashi, Japan.
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140212
PL  - England
TA  - J Neurol Neurosurg Psychiatry
JT  - Journal of neurology, neurosurgery, and psychiatry
JID - 2985191R
RN  - 0 (LYST protein, human)
RN  - 0 (Vesicular Transport Proteins)
SB  - IM
MH  - Asian People/genetics
MH  - Cerebellar Ataxia/complications/genetics
MH  - Chediak-Higashi Syndrome/complications/*genetics
MH  - Genetic Linkage/genetics
MH  - Genetic Predisposition to Disease/genetics
MH  - Genome-Wide Association Study
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Mutation, Missense
MH  - Polymorphism, Single Nucleotide/genetics
MH  - Spastic Paraplegia, Hereditary/complications/*genetics
MH  - Vesicular Transport Proteins/*genetics
OTO - NOTNLM
OT  - CEREBELLAR ATAXIA
OT  - NEUROGENETICS
OT  - NEUROPATHY
OT  - SPASTICITY
EDAT- 2014/02/14 06:00
MHDA- 2014/10/03 06:00
CRDT- 2014/02/14 06:00
PHST- 2014/02/14 06:00 [entrez]
PHST- 2014/02/14 06:00 [pubmed]
PHST- 2014/10/03 06:00 [medline]
AID - jnnp-2013-306981 [pii]
AID - 10.1136/jnnp-2013-306981 [doi]
PST - ppublish
SO  - J Neurol Neurosurg Psychiatry. 2014 Sep;85(9):1024-8. doi: 
      10.1136/jnnp-2013-306981. Epub 2014 Feb 12.