PMID- 37139542
OWN - NLM
STAT- MEDLINE
DCOM- 20230621
LR  - 20231119
IS  - 2328-9503 (Electronic)
IS  - 2328-9503 (Linking)
VI  - 10
IP  - 6
DP  - 2023 Jun
TI  - PLA2G6-associated late-onset parkinsonism in a Sudanese family.
PG  - 983-989
LID - 10.1002/acn3.51781 [doi]
AB  - INTRODUCTION: The phospholipase A2 group VI gene (PLA2G6) encodes an enzyme that 
      catalyzes the hydrolytic release of fatty acids from phospholipids. Four 
      neurological disorders with infantile, juvenile, or early adult-onset are 
      associated with PLA2G6 genetic alterations, namely infantile neuroaxonal 
      dystrophy (INAD), atypical neuroaxonal dystrophy (ANAD), dystonia-parkinsonism 
      (DP), and autosomal recessive early-onset parkinsonism (AREP). Few studies in 
      Africa reported PLA2G6-associated disorders and none with parkinsonism of late 
      adult onset. MATERIAL AND METHODS: The patients were clinically assessed 
      following UK Brain Bank diagnostic criteria and International Parkinson and 
      Movement Disorder Society's Unified Parkinson's Disease Rating Scale (MDS-UPDRS). 
      Brain MRI without contrast was performed. Genetic testing was done using a 
      custom-made Twist panel, screening 34 known genes, 27 risk factors, and 8 
      candidate genes associated with parkinsonism. Filtered variants were 
      PCR-amplified and validated using Sanger sequencing and also tested in additional 
      family members to study their segregation. RESULT: Two siblings born to 
      consanguineous parents developed parkinsonism at the age of 58 and 60 years, 
      respectively. MRI showed an enlarged right hippocampus in patient 2, but no overt 
      abnormalities indicative of INAD or iron deposits. We found two heterozygous 
      variants in PLA2G6, an in-frame deletion NM_003560:c.2070_2072del (p.Val691del) 
      and a missense variant NM_003560:c.956C>T (p.Thr319Met). Both variants were 
      classified as pathogenic. CONCLUSION: This is the first case in which PLA2G6 is 
      associated with late-onset parkinsonism. Functional analysis is needed to confirm 
      the dual effect of both variants on the structure and function of iPLA2beta.
CI  - (c) 2023 The Authors. Annals of Clinical and Translational Neurology published by 
      Wiley Periodicals LLC on behalf of American Neurological Association.
FAU - Bakhit, Yousuf
AU  - Bakhit Y
AUID- ORCID: 0000-0003-3669-7367
AD  - Department of Neurology, University Hospital Bonn, Bonn, Germany.
AD  - Department of Basic Medical Sciences, Faculty of Dentistry, University of 
      Khartoum, Khartoum, Sudan.
AD  - Sudan Neuroscience Projects, University of Khartoum, Khartoum, Sudan.
FAU - Tesson, Christelle
AU  - Tesson C
AD  - Assistance Publique Hopitaux de Paris, Department of Neurology, Pitie-Salpetriere 
      Hospital, Sorbonne Universite, Paris Brain Institute - ICM, Inserm, CNRS, Paris, 
      France.
FAU - Ibrahim, Mohamed O
AU  - Ibrahim MO
AD  - Sudan Neuroscience Projects, University of Khartoum, Khartoum, Sudan.
AD  - Department of Biochemistry, Faculty of Medicine, Sudan University of Science and 
      Technology, Khartoum, Sudan.
FAU - Eltom, Khalid
AU  - Eltom K
AD  - Sudan Neuroscience Projects, University of Khartoum, Khartoum, Sudan.
AD  - Department of Medical Cell Biology, Uppsala Biomedical Center, Uppsala 
      University, Uppsala, Sweden.
FAU - Eltazi, Isra
AU  - Eltazi I
AD  - Department of Neurology, Soba Teaching Hospital, And Department of Medicine, 
      Faculty of Medicine, University of Khartoum, Khartoum, Sudan.
FAU - Elsayed, Liena E O
AU  - Elsayed LEO
AD  - Department of Basic Sciences, College of Medicine, Princess Nourah bint 
      Abdulrahman University, Riyadh, Saudi Arabia.
FAU - Lesage, Suzanne
AU  - Lesage S
AD  - Assistance Publique Hopitaux de Paris, Department of Neurology, Pitie-Salpetriere 
      Hospital, Sorbonne Universite, Paris Brain Institute - ICM, Inserm, CNRS, Paris, 
      France.
FAU - Seidi, Osheik
AU  - Seidi O
AD  - Department of Neurology, Soba Teaching Hospital, And Department of Medicine, 
      Faculty of Medicine, University of Khartoum, Khartoum, Sudan.
FAU - Corvol, Jean-Christophe
AU  - Corvol JC
AD  - Assistance Publique Hopitaux de Paris, Department of Neurology, Pitie-Salpetriere 
      Hospital, Sorbonne Universite, Paris Brain Institute - ICM, Inserm, CNRS, Paris, 
      France.
FAU - Wullner, Ullrich
AU  - Wullner U
AD  - Department of Neurology, University Hospital Bonn, Bonn, Germany.
AD  - German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
CN  - Sudanese Parkinson's Disease Study Group
AD  - Sudan Neuroscience Projects, University of Khartoum, Khartoum, Sudan.
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230503
PL  - United States
TA  - Ann Clin Transl Neurol
JT  - Annals of clinical and translational neurology
JID - 101623278
RN  - EC 3.1.1.4 (Group VI Phospholipases A2)
RN  - EC 3.1.1.4 (PLA2G6 protein, human)
SB  - IM
MH  - Adult
MH  - Humans
MH  - Middle Aged
MH  - *Dystonia/genetics
MH  - *Dystonic Disorders/genetics
MH  - Genetic Testing
MH  - Group VI Phospholipases A2/genetics
MH  - Mutation
MH  - *Parkinsonian Disorders/genetics
PMC - PMC10270271
COIS- The authors declare no conflict of interest.
EDAT- 2023/05/04 06:42
MHDA- 2023/06/19 13:08
PMCR- 2023/05/03
CRDT- 2023/05/04 02:20
PHST- 2023/02/25 00:00 [revised]
PHST- 2022/11/16 00:00 [received]
PHST- 2023/03/27 00:00 [accepted]
PHST- 2023/06/19 13:08 [medline]
PHST- 2023/05/04 06:42 [pubmed]
PHST- 2023/05/04 02:20 [entrez]
PHST- 2023/05/03 00:00 [pmc-release]
AID - ACN351781 [pii]
AID - 10.1002/acn3.51781 [doi]
PST - ppublish
SO  - Ann Clin Transl Neurol. 2023 Jun;10(6):983-989. doi: 10.1002/acn3.51781. Epub 
      2023 May 3.