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Werning, M.* ; Müllner, E.W.* ; Mlynek, G.* ; Dobretzberger, V.* ; Djinovic-Carugo, K.* ; Baron, D.M.* ; Prokisch, H. ; Büchner, B.* ; Klopstock, T.* ; Salzer, U.*

PKAN neurodegeneration and residual PANK2 activities in patient erythrocytes.

Ann. Clin. Transl. Neurol. 7, 1340-1351 (2020)
Publ. Version/Full Text DOI PMC
Open Access Gold
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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. 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. 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. 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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Kinase-associated Neurodegeneration; Pantothenate Kinase; Coenzyme-a; Brain; Iron; Mutations; Blood
ISSN (print) / ISBN 2328-9503
e-ISSN 2328-9503
Journal Annals of Clinical and Translational Neurology
Quellenangaben Volume: 7, Issue: 8, Pages: 1340-1351 Article Number: , Supplement: ,
Publisher Wiley
Publishing Place Chichester [u.a.]
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Human Genetics (IHG)