Partial deficit of pantothenate kinase 2 catalytic activity in a case of tremor-predominant neurodegeneration with brain iron accumulation.
We describe an atypical case of pantothenate kinase-associated neurodegeneration (PKAN) in which slowly progressive arm tremor was the predominant symptom beginning at the age of 25, with late-onset dystonia and dysarthria developing at the age of 50. Compound heterozygous mutations resulting in missense amino acid substitutions G521R and I529V were identified in the pantothenate kinase (PANK2) gene. We demonstrate that while the G521R mutation results in an unstable and inactive protein, the previously unreported I529V substitution has no apparent effect on the stability or catalytic activity of PanK2. The phenotype that results from this combination of mutations suggests that atypical presentations of PKAN may arise from partial deficits in PanK2 catalytic activity.
Liang
Tsao-Wei
TW
Parkinson's Disease Research, Education, and Clinical Center, Philadelphia VA Medical Center and the University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19107, USA. tsao-wei.liang@jefferson.edu
Truax
Adam C
AC
Trojanowski
John Q
JQ
Lee
Virginia M-Y
VM
Stern
Matthew B
MB
Kotzbauer
Paul T
PT
D001120:Arginine / Q000235:genetics; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D004252:DNA Mutational Analysis / Q000379:methods; D005998:Glycine / Q000235:genetics; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007532:Isoleucine / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D019636:Neurodegenerative Diseases / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000172:deficiency* / Q000235:genetics; D014202:Tremor / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D014633:Valine / Q000235:genetics
D007532:Isoleucine; D001120:Arginine; D007501:Iron; D017853:Phosphotransferases (Alcohol Group Acceptor); C023088:pantothenate kinase; D014633:Valine; D005998:Glycine