PMID- 30738281
OWN - NLM
STAT- MEDLINE
DCOM- 20190826
LR  - 20190826
IS  - 2211-0356 (Electronic)
IS  - 2211-0348 (Linking)
VI  - 30
DP  - 2019 May
TI  - Intra-family phenotype variations in familial neuromyelitis optica spectrum 
      disorders.
PG  - 57-62
LID - S2211-0348(19)30058-6 [pii]
LID - 10.1016/j.msard.2019.02.002 [doi]
AB  - BACKGROUND: The aim of the current study was to examine intra-family phenotype 
      variations in familial neuromyelitis optica (NMO) spectrum disorder. METHODS: The 
      clinical presentation and neuroimaging features of two family members (mother and 
      daughter) from a NMO spectrum disorder family (index family) were analyzed. 
      Multiplex polymerase chain reaction was performed based on targeted re-sequencing 
      on the AQP4 gene and the human leukocyte antigen (HLA) loci. The clinical and 
      neuroimaging features of the members of six other previously reported NMO 
      spectrum disorder families were also included for analysis. RESULTS: In the core 
      family, the mother was aged 39 at disease onset and the initial presentation was 
      spinal cord involvement, whereas the daughter was 22 years old at disease onset 
      and the initial presentation was brainstem involvement. No coding pathogenic 
      variants or single nucleotide polymorphisms of the AQP4 gene were identified in 
      the mother, daughter or father. As for HLA genotyping, the HLA-DRB1*03 and 
      HLA-DPB1*04 alleles were shared by the mother and daughter. The HLA-DPB1*05 was 
      present in the affected daughter and was inherited from the unaffected father. As 
      for the other six reported families with familial NMO spectrum disorder, four 
      mother-daughter pairs had a different age at disease onset and/or a different 
      initial presentation. The other two affected family groups were sister-sister 
      pairs; they had a similar age of onset and similar initial presentations. 
      CONCLUSION: The present study offers a preliminary view of the clinical and 
      neuroimaging features of patients with familial NMO spectrum disorder. Clinical 
      heterogeneities were found among the family members, especially the mother and 
      daughter pairs. The presence of risk allele HLA-DR*03:01 may be an important 
      genetic finding for familial NMO spectrum disorder patients. To the best of our 
      knowledge, this clinical heterogeneity has not been previously examined or 
      reported in the literature. For better delineation of the intra-familial 
      phenotype variations in familial NMO spectrum disorder, further large-scale 
      studies are needed.
CI  - Copyright (c) 2019. Published by Elsevier B.V.
FAU - Lee, Jun-Jun
AU  - Lee JJ
AD  - Department of Neurology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung 
      University, College of Medicine, Kaohsiung, Taiwan; Department of Information 
      Management, National Sun Yat-sen University, Kaohsiung, Taiwan.
FAU - Tsai, Meng-Han
AU  - Tsai MH
AD  - Department of Neurology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung 
      University, College of Medicine, Kaohsiung, Taiwan.
FAU - Lien, Chia-Yi
AU  - Lien CY
AD  - Department of Neurology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung 
      University, College of Medicine, Kaohsiung, Taiwan.
FAU - Huang, Yu-Ju
AU  - Huang YJ
AD  - Department of Neurology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung 
      University, College of Medicine, Kaohsiung, Taiwan.
FAU - Chang, Wen-Neng
AU  - Chang WN
AD  - Department of Neurology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung 
      University, College of Medicine, Kaohsiung, Taiwan. Electronic address: 
      cwenneng@ms19.hinet.net.
LA  - eng
PT  - Journal Article
DEP - 20190204
PL  - Netherlands
TA  - Mult Scler Relat Disord
JT  - Multiple sclerosis and related disorders
JID - 101580247
RN  - 0 (HLA-D Antigens)
MH  - Adult
MH  - Aged
MH  - Female
MH  - HLA-D Antigens/*genetics
MH  - Humans
MH  - Middle Aged
MH  - Neuromyelitis Optica/*diagnostic imaging/*genetics/*physiopathology
MH  - Pedigree
MH  - Phenotype
MH  - Young Adult
OTO - NOTNLM
OT  - AQP4 gene
OT  - Familial
OT  - HLA genotype
OT  - NMO spectrum disorder
OT  - Phenptype variation
EDAT- 2019/02/10 06:00
MHDA- 2019/08/27 06:00
CRDT- 2019/02/10 06:00
PHST- 2019/01/12 00:00 [received]
PHST- 2019/02/03 00:00 [accepted]
PHST- 2019/02/10 06:00 [pubmed]
PHST- 2019/08/27 06:00 [medline]
PHST- 2019/02/10 06:00 [entrez]
AID - S2211-0348(19)30058-6 [pii]
AID - 10.1016/j.msard.2019.02.002 [doi]
PST - ppublish
SO  - Mult Scler Relat Disord. 2019 May;30:57-62. doi: 10.1016/j.msard.2019.02.002. 
      Epub 2019 Feb 4.