Dataset Information

Clinical heterogeneity of PLA2G6-related Parkinsonism: analysis of two Saudi families.

ABSTRACT:

Background

Recessive mutations in PLA2G6 have been associated with different neurodegenerative disorders, including infantile neuroaxonal dystrophy, neurodegeneration with brain iron accumulation and more recently, early-onset dystonia parkinsonism.

Method

Targeted-next generation sequencing using a custom Neurology panel, containing 758 OMIM-listed genes implicated in neurological disorders, was carried out in two index cases from two different Saudi families displaying early-onset levodopa-responsive Parkinsonism with pyramidal signs and additional clinical features. The detected mutations were verified in the index cases and available family members by direct sequencing.

Results and conclusion

We identified a previously described PLA2G6 homozygous p.R741Q mutation in three affected and two asymptomatic individuals from two Saudi families. Our finding reinforces the notion of the broadness of the clinical spectrum of PLA2G6-related neurodegeneration.

SUBMITTER: Bohlega SA

PROVIDER: S-EPMC4897907 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Publications

Clinical heterogeneity of PLA2G6-related Parkinsonism: analysis of two Saudi families.

Bohlega Saeed A SA Al-Mubarak Bashayer R BR Alyemni Eman A EA Abouelhoda Mohamed M Monies Dorota D Mustafa Abeer E AE Khalil Dania S DS Al Haibi Sara S Abou Al-Shaar Hussam H Faquih Tariq T El-Kalioby Mohamed M Tahir Asma I AI Al Tassan Nada A NA

BMC research notes 20160607

<h4>Background</h4>Recessive mutations in PLA2G6 have been associated with different neurodegenerative disorders, including infantile neuroaxonal dystrophy, neurodegeneration with brain iron accumulation and more recently, early-onset dystonia parkinsonism.<h4>Method</h4>Targeted-next generation sequencing using a custom Neurology panel, containing 758 OMIM-listed genes implicated in neurological disorders, was carried out in two index cases from two different Saudi families displaying early-ons ...[more]

PMID: 27268037

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Project description:IntroductionPhospholipase A2 Group VI (PLA2G6), encoding calcium-independent phospholipase A2, has been isolated as the gene responsible for an autosomal recessive form of early-onset Parkinson's disease (namely, PARK14). Compared to idiopathic Parkinson's disease (iPD), PARK14 has several atypical clinical features. PARK14 has an earlier age at onset and is more likely to develop levodopa-induced dyskinesia. In iPD, serum metabolomics has observed alterations in several metabolic pathways that are related to disease status and clinical manifestations. This study aims to describe the serum metabolomics features of patients with PARK14.DesignThis case-control biomarker study tested nine patients diagnosed with PARK14. Eight age and sex-matched healthy subjects were recruited as controls. To evaluate the influence of single heterozygous mutation, we enrolled eight healthy one-degree family members of patients with PARK14, two patients diagnosed with early-onset Parkinson's disease (EOPD) who had only a single heterozygous PLA2G6 mutation, and one patient with EOPD without any known pathogenic mutation.MethodsThe diagnosis of PARK14 was made according to the diagnostic criteria for Parkinson's disease (PD) and confirmed by genetic testing. To study the serum metabolic features, we analyzed participants' serum using UHPLC-QTOF/MS analysis, a well-established technology.ResultsWe quantified 50 compounds of metabolites from the serum of all the study subjects. Metabolites alterations in serum had good predictive accuracy for PARK14 diagnosis (AUC 0.903) and advanced stage in PARK14 (AUC 0.944). Of the 24 metabolites that changed significantly in patients' serum, eight related to lipid metabolism. Oleic acid and xanthine were associated with MMSE scores. Xanthine, L-histidine, and phenol correlated with UPDRS-III scores. Oleic acid and 1-oleoyl-L-alpha-lysophosphatidic acid could also predict the subclass of the more advanced stage in the PLA2G6 Group in ROC models.ConclusionThe significantly altered metabolites can be used to differentiate PLA2G6 pathogenic mutations and predict disease severity. Patients with PLA2G6 mutations had elevated lipid compounds in C18:1 and C16:0 groups. The alteration of lipid metabolism might be the key intermediate process in PLA2G6-related disease that needs further investigation.

Dataset Information

Clinical heterogeneity of PLA2G6-related Parkinsonism: analysis of two Saudi families.

Background

Method

Results and conclusion

Publications

Clinical heterogeneity of PLA2G6-related Parkinsonism: analysis of two Saudi families.

Similar Datasets

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