M.B.H. and K. H. contributed equally to this study.
Genotypic and phenotypic spectrum of PANK2 mutations in patients with neurodegeneration with brain iron accumulation
Article first published online: 25 JAN 2006
Copyright © 2006 American Neurological Association
Annals of Neurology
Volume 59, Issue 2, pages 248–256, February 2006
How to Cite
Hartig, M. B., Hörtnagel, K., Garavaglia, B., Zorzi, G., Kmiec, T., Klopstock, T., Rostasy, K., Svetel, M., Kostic, V. S., Schuelke, M., Botz, E., Weindl, A., Novakovic, I., Nardocci, N., Prokisch, H. and Meitinger, T. (2006), Genotypic and phenotypic spectrum of PANK2 mutations in patients with neurodegeneration with brain iron accumulation. Ann Neurol., 59: 248–256. doi: 10.1002/ana.20771
- Issue published online: 25 JAN 2006
- Article first published online: 25 JAN 2006
- Manuscript Accepted: 27 OCT 2005
- Manuscript Revised: 19 OCT 2005
- Manuscript Received: 9 AUG 2005
- Bioinformatics for the Functional Analysis of Mammalian Genomes (BFAM) project from the German Federal Ministry of Education and Research. Grant Number: 031U112C
- German National Genome Network (German Ministry for Education and Research). Grant Numbers: 01GS0116, 01GR0411
- Italian National Ministry of Health (RF ex art.56)
- Paolo Zorzi Association for Neuroscience
Neurodegeneration with brain iron accumulation (NBIA) is a group of disorders characterized by magnetic resonance imaging (MRI) changes in basal ganglia. Both missense and nonsense mutations have been found in such patients in a gene encoding the mitochondrial pantothenate kinase (PANK2).
We completed a mutation screen in 72 patients with the diagnosis NBIA based on clinical findings and radiological imaging. The entire coding region of the PANK2 gene (20p12.3) was investigated for point mutations and deletions.
We uncovered both mutant alleles in 48 patients. Deletions accounted for 4% of mutated alleles. Patients with two loss-of-function alleles (n = 11) displayed symptoms always at an early stage of life. In the presence of missense mutations (n = 37), the age of onset correlated with residual activity of the pantothenate kinase. Progression of disease measured by loss of ambulation was variable in both groups. We did not observe a strict correlation between the eye-of-the-tiger sign and PANK2 mutations. In 24 patients, no PANK2 mutation was identified.
Deletion screening of PANK2 should be part of the diagnostic spectrum. Factors other than enzymatic residual activity are determining the course of disease. There are strong arguments in favor of locus heterogeneity. Ann Neurol 2006;59:248–256