Document Detail

Neurological symptoms, genotype-phenotype correlations and ethnic-specific differences in Bulgarian patients with Wilson disease.
MedLine Citation:
PMID:  22735241     Owner:  NLM     Status:  MEDLINE    
OBJECTIVES: The aim of our study was to characterize the neurological symptoms in Bulgarian patients with Wilson disease (WD), to investigate genotype-phenotype correlations, and to test whether there are differences in phenotype between patients of different ethnic origin.
PATIENTS AND METHODS: A total of 126 Bulgarian patients with WD were included in the study. Detailed history, physical and neurological examination, laboratory investigation of copper metabolism, slit-lamp examination, abdominal ultrasound, magnetic resonance imaging/computed tomography of the brain, molecular genetic testing, and statistical analysis were performed.
RESULTS: Eighty-two patients demonstrated neurological signs. Tremor and dysarthria were most frequently observed. Rigidity, bradykinesia, and pyramidal signs were found in >25% of the patients. Dystonia, chorea, athetosis, ballismus, and epilepsy were rarely observed. We identified a total of 27 mutations of ATP7B. The most frequent mutation is p.H1069Q found on at least 1 allele in 78% of the patients. We did not find a significant correlation between p.H1069Q homozygosity and age of onset, ceruloplasmin level, and urinary copper excretion. The patients homozygous for p.H1069Q presented more frequently with hepatic signs. Mutations predicted to cause production of truncated protein are associated with earlier age at onset and lower ceruloplasmin level. In contrast to Bulgarian patients, Roma patients had an earlier disease onset and more frequent hepatic manifestation.
CONCLUSIONS: WD presents with a variety of neurological signs. The mutation p.H1069Q is not uniformly associated with late onset and neurological presentation. Frameshift and nonsense mutations lead to severe phenotype. There are ethnic-specific differences in disease manifestation.
Violeta Mihaylova; Teodor Todorov; Hristo Jelev; Iskren Kotsev; Ludmila Angelova; Olga Kosseva; Georgi Georgiev; Ralica Ganeva; Silvia Cherninkova; Ludmila Tankova; Aleksei Savov; Ivailo Tournev
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The neurologist     Volume:  18     ISSN:  2331-2637     ISO Abbreviation:  Neurologist     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-06-27     Completed Date:  2012-10-29     Revised Date:  2014-11-05    
Medline Journal Info:
Nlm Unique ID:  9503763     Medline TA:  Neurologist     Country:  United States    
Other Details:
Languages:  eng     Pagination:  184-9     Citation Subset:  IM    
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MeSH Terms
Adenosine Triphosphatases / genetics
Brain / pathology
Bulgaria / ethnology
Cation Transport Proteins / genetics
Genetic Association Studies*
Hepatolenticular Degeneration / ethnology*,  genetics*,  physiopathology
Middle Aged
Young Adult
Reg. No./Substance:
0/Cation Transport Proteins; EC 3.6.1.-/Adenosine Triphosphatases; EC disease protein

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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