Parkin mRNA Expression Levels in Peripheral Blood Mononuclear Cells in Parkin-Related Parkinson's Disease.
Mov Disord
; 39(4): 715-722, 2024 Apr.
Article
en En
| MEDLINE
| ID: mdl-38357851
ABSTRACT
INTRODUCTION:
Pathogenic variants in parkin (PRKN gene) are the second most prevalent known monogenic cause of Parkinson's disease (PD). How monoallelic or biallelic pathogenic variants in the PRKN gene may affect its transcription in patient-derived biological material has not been systematically studied.METHODS:
PRKN mRNA expression levels were measured with real-time polymerase chain reaction (RT-PCR) in peripheral blood mononuclear cells (PBMCs). PBMCs were derived from PRKN-mutated PD patients (PRKN-PD) (n = 12), sporadic PD (sPD) (n = 21) and healthy controls (n = 21). Six of the PRKN-PD patients were heterozygous, four were compound heterozygous, and two were homozygous for PRKN variants.RESULTS:
A statistically significant decrease in PRKN expression levels was present, compared to healthy controls and sPD, in heterozygous (P = 0.019 and 0.031 respectively) and biallelic (P < 0.001 for both) PRKN-PD. PRKN expression levels in biallelic PD patients were uniformly very low and were reduced, albeit not significantly, compared to heterozygotes. Based on receiver operating characteristic analysis, low PRKN expression levels were a sensitive and extremely specific indicator for the presence of PRKN pathogenic variants.CONCLUSIONS:
Assessment of PRKN mRNA levels in PBMCs may be a useful way to screen for biallelic pathogenic variants in the PRKN gene. Suspicion for certain variants in a heterozygous state may also be raised based on low PRKN mRNA levels. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedad de Parkinson
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ARN Mensajero
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Leucocitos Mononucleares
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Ubiquitina-Proteína Ligasas
Límite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Mov Disord
Asunto de la revista:
NEUROLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Grecia