PMID- 18799783
OWN - NLM
STAT- MEDLINE
DCOM- 20081222
LR  - 20211020
IS  - 1526-632X (Electronic)
IS  - 0028-3878 (Print)
IS  - 0028-3878 (Linking)
VI  - 71
IP  - 18
DP  - 2008 Oct 28
TI  - Neurodegeneration associated with genetic defects in phospholipase A(2).
PG  - 1402-9
LID - 10.1212/01.wnl.0000327094.67726.28 [doi]
AB  - OBJECTIVE: Mutations in the gene encoding phospholipase A(2) group VI (PLA2G6) 
      are associated with two childhood neurologic disorders: infantile neuroaxonal 
      dystrophy (INAD) and idiopathic neurodegeneration with brain iron accumulation 
      (NBIA). INAD is a severe progressive psychomotor disorder in which axonal 
      spheroids are found in brain, spinal cord, and peripheral nerves. High globus 
      pallidus iron is an inconsistent feature of INAD; however, it is a diagnostic 
      criterion of NBIA, which describes a clinically and genetically heterogeneous 
      group of disorders that share this hallmark feature. We sought to delineate the 
      clinical, radiographic, pathologic, and genetic features of disease resulting 
      from defective phospholipase A(2). METHODS: We identified 56 patients clinically 
      diagnosed with INAD and 23 with idiopathic NBIA and screened their DNA for PLA2G6 
      mutations. RESULTS: Eighty percent of patients with INAD had mutations in PLA2G6, 
      whereas mutations were found in only 20% of those with idiopathic NBIA. All 
      patients with two null mutations had a more severe phenotype. On MRI, nearly all 
      mutation-positive patients had cerebellar atrophy, and half showed brain iron 
      accumulation. We observed Lewy bodies and neurofibrillary tangles in association 
      with PLA2G6 mutations. CONCLUSION: Defects in phospholipase A(2) lead to a range 
      of phenotypes. PLA2G6 mutations are associated with nearly all cases of classic 
      infantile neuroaxonal dystrophy but a minority of cases of idiopathic 
      neurodegeneration with brain iron accumulation, and genotype correlates with 
      phenotype. Cerebellar atrophy predicts which patients are likely to be 
      mutation-positive. The neuropathologic changes that are caused by defective 
      phospholipase A(2) suggest a shared pathogenesis with both Parkinson and 
      Alzheimer diseases.
FAU - Gregory, A
AU  - Gregory A
AD  - Department of Molecular and Medical Genetics, Oregon Health & Science University, 
      L103a, 3181 SW Sam Jackson Park Rd., Portland, OR 97239-3098, USA.
FAU - Westaway, S K
AU  - Westaway SK
FAU - Holm, I E
AU  - Holm IE
FAU - Kotzbauer, P T
AU  - Kotzbauer PT
FAU - Hogarth, P
AU  - Hogarth P
FAU - Sonek, S
AU  - Sonek S
FAU - Coryell, J C
AU  - Coryell JC
FAU - Nguyen, T M
AU  - Nguyen TM
FAU - Nardocci, N
AU  - Nardocci N
FAU - Zorzi, G
AU  - Zorzi G
FAU - Rodriguez, D
AU  - Rodriguez D
FAU - Desguerre, I
AU  - Desguerre I
FAU - Bertini, E
AU  - Bertini E
FAU - Simonati, A
AU  - Simonati A
FAU - Levinson, B
AU  - Levinson B
FAU - Dias, C
AU  - Dias C
FAU - Barbot, C
AU  - Barbot C
FAU - Carrilho, I
AU  - Carrilho I
FAU - Santos, M
AU  - Santos M
FAU - Malik, I
AU  - Malik I
FAU - Gitschier, J
AU  - Gitschier J
FAU - Hayflick, S J
AU  - Hayflick SJ
LA  - eng
GR  - R01 HD050832-01A1/HD/NICHD NIH HHS/United States
GR  - UL1 RR024140-01/RR/NCRR NIH HHS/United States
GR  - R01 EY012353/EY/NEI NIH HHS/United States
GR  - R01 EY012353-09/EY/NEI NIH HHS/United States
GR  - GTF04002/TI_/Telethon/Italy
GR  - R01 HD050832/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20080917
PL  - United States
TA  - Neurology
JT  - Neurology
JID - 0401060
RN  - E1UOL152H7 (Iron)
RN  - EC 3.1.1.4 (Group VI Phospholipases A2)
RN  - EC 3.1.1.4 (PLA2G6 protein, human)
SB  - IM
CIN - Neurology. 2009 Sep 8;73(10):819. PMID: 19738181
MH  - Adolescent
MH  - Brain/*metabolism
MH  - Child
MH  - Child, Preschool
MH  - DNA Mutational Analysis
MH  - Family Health
MH  - Female
MH  - *Genetic Predisposition to Disease
MH  - Group VI Phospholipases A2/*genetics
MH  - Humans
MH  - Iron/*metabolism
MH  - Magnetic Resonance Imaging/methods
MH  - Male
MH  - *Mutation
MH  - Neurodegenerative Diseases/diagnostic imaging/*genetics/*pathology
MH  - Radionuclide Imaging
PMC - PMC2676964
EDAT- 2008/09/19 09:00
MHDA- 2008/12/23 09:00
PMCR- 2009/10/28
CRDT- 2008/09/19 09:00
PHST- 2008/09/19 09:00 [pubmed]
PHST- 2008/12/23 09:00 [medline]
PHST- 2008/09/19 09:00 [entrez]
PHST- 2009/10/28 00:00 [pmc-release]
AID - 01.wnl.0000327094.67726.28 [pii]
AID - znl04208001402 [pii]
AID - 10.1212/01.wnl.0000327094.67726.28 [doi]
PST - ppublish
SO  - Neurology. 2008 Oct 28;71(18):1402-9. doi: 10.1212/01.wnl.0000327094.67726.28. 
      Epub 2008 Sep 17.