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PKAN neurodegeneration and residual PANK2 activities in patient erythrocytes.
- Source :
-
Annals of clinical and translational neurology [Ann Clin Transl Neurol] 2020 Aug; Vol. 7 (8), pp. 1340-1351. Date of Electronic Publication: 2020 Jul 23. - Publication Year :
- 2020
-
Abstract
- Objective: Pantothenate kinase 2-associated neurodegeneration (PKAN) is a rare neurodegenerative disease caused by mutations in the pantothenate kinase 2 (PANK2) gene. PKAN is associated with iron deposition in the basal ganglia and, occasionally, with the occurrence of misshaped erythrocytes (acanthocytes). The aim of this study was to assess residual activity of PANK2 in erythrocytes of PKAN patients and to correlate these data with the type of PANK2 mutations and the progression of neurodegeneration.<br />Methods: Residual PANK2 activities in erythrocytes of 14 PKAN patients and 14 related carriers were assessed by a radiometric assay. Clinical data on neurodegeneration included the Barry-Albright Dystonia Scale (BAD-Scale) besides further general patient features. A molecular visualization and analysis program was used to rationalize the influence of the PKAN causing mutations on a molecular level.<br />Results: Erythrocytes of PKAN patients had markedly reduced or no PANK2 activity. However, patients with at least one allele of the c.1583C > T (T528M) or the c.833G > T (R278L) variant exhibited 12-56% of residual PANK2 activity. In line, molecular modeling indicated only minor effects on enzyme structure for these point mutations. On average, these patients with c.1583C > T or c.833G > T variant had lower BAD scores corresponding to lower symptom severity than patients with other PANK2 point mutations.<br />Interpretation: Residual erythrocyte PANK2 activity could be a predictor for the progression of neurodegeneration in PKAN patients. Erythrocytes are an interesting patient-derived cell system with still underestimated diagnostic potential.<br /> (© 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)
- Subjects :
- Adolescent
Adult
Biological Specimen Banks
Female
Humans
Male
Pantothenate Kinase-Associated Neurodegeneration genetics
Pantothenate Kinase-Associated Neurodegeneration pathology
Phosphotransferases (Alcohol Group Acceptor) genetics
Prognosis
Young Adult
Disease Progression
Erythrocytes metabolism
Pantothenate Kinase-Associated Neurodegeneration blood
Pantothenate Kinase-Associated Neurodegeneration diagnosis
Phosphotransferases (Alcohol Group Acceptor) metabolism
Registries
Subjects
Details
- Language :
- English
- ISSN :
- 2328-9503
- Volume :
- 7
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Annals of clinical and translational neurology
- Publication Type :
- Academic Journal
- Accession number :
- 32705819
- Full Text :
- https://doi.org/10.1002/acn3.51127