Association Between Peroxisomal Biogenesis Factor 7 and Autism Spectrum Disorders in a Korean Population

Ro, MyungJa; Park, JungWon; Nam, Min; Bang, Hee Jung; Yang, Jae Won; Choi, Kyung-Sik; Kim, Su Kang; Chung, Joo‐Ho; Kwack, KyuBum

doi:10.1177/0883073811435507

Cited by 11 publications

(5 citation statements)

References 31 publications

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“…The consortium behind that study identified a mutation affecting the WD‐40 domain of PEX7 in three affected children, but not in the nonaffected siblings, of consanguineous parents. This discovery supports the findings in an earlier paper, which proposed an association between single nucleotide polymorphisms in PEX7 and autism . Furthermore, retrospective screening of the clinical records of previously reported RCDP patients revealed that two patients with less severe disease course had later been diagnosed with a neurodevelopmental condition (autism and attention deficit hyperactivity disorder) .…”

Section: Potential Involvement Of Ether Lipids In More Common Neurolosupporting

confidence: 89%

From peroxisomal disorders to common neurodegenerative diseases – the role of ether phospholipids in the nervous system

2017

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The emerging diverse roles of ether (phospho)lipids in nervous system development and function in health and disease are currently attracting growing interest. Plasmalogens, a subgroup of ether lipids, are important membrane components involved in vesicle fusion and membrane raft composition. They store polyunsaturated fatty acids and may serve as antioxidants. Ether lipid metabolites act as precursors for the formation of glycosyl-phosphatidyl-inositol anchors; others, like platelet-activating factor, are implicated in signaling functions. Consolidating the available information, we attempt to provide molecular explanations for the dramatic neurological phenotype in ether lipid-deficient human patients and mice by linking individual functional properties of ether lipids with pathological features. Furthermore, recent publications have identified altered ether lipid levels in the context of many acquired neurological disorders including Alzheimer's disease (AD) and autism. Finally, current efforts to restore ether lipids in peroxisomal disorders as well as AD are critically reviewed.

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Section: Potential Involvement Of Ether Lipids In More Common Neurolosupporting

confidence: 89%

From peroxisomal disorders to common neurodegenerative diseases – the role of ether phospholipids in the nervous system

2017

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“…In 2013, a study applying whole exome sequencing identified a link between mutations in PEX7 (RCDP type 1) and autism spectrum disorder, a range of neurodevelopmental conditions characterized by deficits in communication and social interaction and repetitive behavior, in a family with three affected children [256]. This observation supports previous work showing an association between single nucleotide polymorphisms in the PEX7 gene and autism [257]. Prompted by their findings, the authors reviewed previously reported RCDP cases for potential signs of autism and found two further patients, which had later been diagnosed with neurodevelopmental conditions (one with autism, the other with attention deficit hyperactivity disorder) [256].…”

Section: The Contribution Of Peroxisomes To More Common Neurological supporting

confidence: 57%

Peroxisomes in brain development and function

Berger

Dorninger

Forss‐Petter

et al. 2016

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

145

123

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Peroxisomes contain numerous enzymatic activities that are important for mammalian physiology. Patients lacking either all peroxisomal functions or a single enzyme or transporter function typically develop severe neurological deficits, which originate from aberrant development of the brain, demyelination and loss of axonal integrity, neuroinflammation or other neurodegenerative processes. Whilst correlating peroxisomal properties with a compilation of pathologies observed in human patients and mouse models lacking all or individual peroxisomal functions, we discuss the importance of peroxisomal metabolites and tissue- and cell type-specific contributions to the observed brain pathologies. This enables us to deconstruct the local and systemic contribution of individual metabolic pathways to specific brain functions. We also review the recently discovered variability of pathological symptoms in cases with unexpectedly mild presentation of peroxisome biogenesis disorders. Finally, we explore the emerging evidence linking peroxisomes to more common neurological disorders such as Alzheimer’s disease, autism and amyotrophic lateral sclerosis. This article is part of a Special Issue entitled: Peroxisomes edited by Ralf Erdmann.

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“…This hypothesis is now supported by various observations, including the identification of reduced plasmalogen levels in the blood of autistic patients [34], and reports about clinical diagnoses of ASD and ADHD in patients with RCDP [17,35]. The genetic link between PEX7 and ASD, as proposed in two recent publications [17,36], further adds to these findings. Even more, de novo mutations in another ether lipid-metabolizing enzyme, alkylglycerol monooxygenase, have been identified in autistic patients by two independent studies [37,38].…”

Section: Discussionmentioning

confidence: 62%

Ether Lipid Deficiency in Mice Produces a Complex Behavioral Phenotype Mimicking Aspects of Human Psychiatric Disorders

Dorninger

Gundacker

Zeitler

et al. 2019

IJMS

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Ether lipids form a specialized subgroup of phospholipids that requires peroxisomes to be synthesized. We have previously detected that deficiency in these lipids leads to a severe disturbance of neurotransmitter homeostasis and release as well as behavioral abnormalities, such as hyperactivity, in a mouse model. Here, we focused on a more detailed examination of the behavioral phenotype of ether lipid-deficient mice (Gnpat KO) and describe a set of features related to human psychiatric disorders. Gnpat KO mice show strongly impaired social interaction as well as nestlet shredding and marble burying, indicating disturbed execution of inborn behavioral patterns. Also, compromised contextual and cued fear conditioning in these animals suggests a considerable memory deficit, thus potentially forming a connection to the previously determined ether lipid deficit in human patients with Alzheimer’s disease. Nesting behavior and the preference for social novelty proved normal in ether lipid-deficient mice. In addition, we detected task-specific alterations in paradigms assessing depression- and anxiety-related behavior. The reported behavioral changes may be used as easy readout for the success of novel treatment strategies against ether lipid deficiency in ameliorating nervous system-associated symptoms. Furthermore, our findings underline that ether lipids are paramount for brain function and demonstrate their relevance for cognitive, social, and emotional behavior. We hereby substantially extend previous observations suggesting a link between deficiency in ether lipids and human mental illnesses, particularly autism and attention-deficit hyperactivity disorder.

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Association Between Peroxisomal Biogenesis Factor 7 and Autism Spectrum Disorders in a Korean Population

Cited by 11 publications

References 31 publications

From peroxisomal disorders to common neurodegenerative diseases – the role of ether phospholipids in the nervous system

From peroxisomal disorders to common neurodegenerative diseases – the role of ether phospholipids in the nervous system

Peroxisomes in brain development and function

Ether Lipid Deficiency in Mice Produces a Complex Behavioral Phenotype Mimicking Aspects of Human Psychiatric Disorders

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