PMID- 34168672
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220424
IS  - 1664-8021 (Print)
IS  - 1664-8021 (Electronic)
IS  - 1664-8021 (Linking)
VI  - 12
DP  - 2021
TI  - New Insights of Phospholipase A2 Associated Neurodegeneration Phenotype Based on 
      the Long-Term Follow-Up of a Large Hungarian Family.
PG  - 628904
LID - 10.3389/fgene.2021.628904 [doi]
LID - 628904
AB  - INTRODUCTION: Phospholipase A2-associated Neurodegeneration (PLAN) is a group of 
      neurodegenerative diseases associated with the alterations of PLA2G6. Some 
      phenotype-genotype association are well known but there is no clear explanation 
      why some cases can be classified into distinct subgroups, while others follow a 
      continuous clinical spectrum. METHODS: Long-term neurological, and psychiatric 
      follow-up, neuropathological, radiological, and genetic examinations, were 
      performed in three affected girls and their family. RESULTS: Two 24-years old 
      twins and their 22-years old sister harbored the p.P622S, and p.R600W mutation in 
      PLA2G6. The age of onset and the most prominent presenting symptoms (gaze palsy, 
      ataxia, dystonia, psychomotor regression indicated atypical neuroaxonal dystrophy 
      (ANAD), however, optic atrophy, severe tetraparesis would fit into infantile 
      neuroaxonal dystrophy (INAD). All siblings had hyperintensity in the globi 
      pallidi and substantiae nigrae which is reported in ANAD, whereas it is 
      considered a later neuroradiological marker in INAD. The slow progression, 
      rigidity, bradykinesis, and the prominent psychiatric symptoms indicate 
      PLA2G6-related dystonia-parkinsonism. Abnormal mitochondria, lipid accumulation 
      and axonal spheroids were observed in the muscle and nerve tissue. Brain 
      deposition appeared 6 years following the initial cerebellar atrophy. Mild MRI 
      alterations were detected in the asymptomatic carrier parents. CONCLUSION: The 
      colorful clinical symptoms, the slightly discordant phenotype, and the 
      neuroimaging data in the family supports the view that despite the distinct 
      definition of age-related phenotypes in PLAN, these are not strict disease 
      categories, but rather a continuous phenotypic spectrum. The mild MRI alterations 
      of the parents and the family history suggest that even heterozygous pathogenic 
      variants might be associated with clinical symptoms, although systematic study is 
      needed to prove this.
CI  - Copyright (c) 2021 Toth-Bencsik, Balicza, Varga, Lengyel, Rudas, Gal and Molnar.
FAU - Toth-Bencsik, Renata
AU  - Toth-Bencsik R
AD  - Institute of Genomic Medicine and Rare Disorders, Semmelweis University, 
      Budapest, Hungary.
FAU - Balicza, Peter
AU  - Balicza P
AD  - Institute of Genomic Medicine and Rare Disorders, Semmelweis University, 
      Budapest, Hungary.
FAU - Varga, Edina Timea
AU  - Varga ET
AD  - Department of Neurology, Albert Szent-Gyorgyi Medical and Pharmaceutical Center, 
      University of Szeged, Szeged, Hungary.
FAU - Lengyel, Andras
AU  - Lengyel A
AD  - Institute of Genomic Medicine and Rare Disorders, Semmelweis University, 
      Budapest, Hungary.
FAU - Rudas, Gabor
AU  - Rudas G
AD  - MR Research Center, Semmelweis University, Budapest, Hungary.
FAU - Gal, Aniko
AU  - Gal A
AD  - Institute of Genomic Medicine and Rare Disorders, Semmelweis University, 
      Budapest, Hungary.
FAU - Molnar, Maria Judit
AU  - Molnar MJ
AD  - Institute of Genomic Medicine and Rare Disorders, Semmelweis University, 
      Budapest, Hungary.
LA  - eng
PT  - Journal Article
DEP - 20210608
PL  - Switzerland
TA  - Front Genet
JT  - Frontiers in genetics
JID - 101560621
PMC - PMC8217829
OTO - NOTNLM
OT  - Dystonia-Parkinsonism syndrome
OT  - PLA2G6 gene
OT  - PLA2G6-associated neurodegeneration (PLAN)
OT  - neuroaxonal dystrophy
OT  - neurodegeneration with brain iron accumulation II (NBIA2B)
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/06/26 06:00
MHDA- 2021/06/26 06:01
PMCR- 2021/06/08
CRDT- 2021/06/25 06:50
PHST- 2020/11/13 00:00 [received]
PHST- 2021/04/06 00:00 [accepted]
PHST- 2021/06/25 06:50 [entrez]
PHST- 2021/06/26 06:00 [pubmed]
PHST- 2021/06/26 06:01 [medline]
PHST- 2021/06/08 00:00 [pmc-release]
AID - 10.3389/fgene.2021.628904 [doi]
PST - epublish
SO  - Front Genet. 2021 Jun 8;12:628904. doi: 10.3389/fgene.2021.628904. eCollection 
      2021.