Carta Revisado por pares

Mutational analysis of COASY in an Italian patient with NBIA

2016; Elsevier BV; Volume: 28; Linguagem: Inglês

10.1016/j.parkreldis.2016.03.011

ISSN

1873-5126

Autores

Grazia Annesi, Monica Gagliardi, Grazia Iannello, Aldo Quattrone, Grazia Iannello, Aldo Quattrone,

Tópico(s)

Metabolism and Genetic Disorders

Resumo

Neurodegeneration with brain iron accumulation (NBIA) comprises a clinically and genetically heterogeneous group of neurodegenerative diseases characterized by progressive degeneration of the central nervous system and iron accumulation, particularly within the globus pallidus [ [1] Schneider S.A. Neurodegeneration with brain iron accumulation. Park. Relat. Disord. 2016; 22: S21-S25 Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar ]. They clinically present as hypo- and/or hyperkinetic movement disorders and a variable degree of pyramidal, cerebellar, peripheral nerve, autonomic, cognitive and psychiatric involvement and visual dysfunction. Several causative genes underlying NBIA have been identified which explain about 65% of cases. These genes, including PANK2, PLA2G6, C19orf12, FA2H, ATP13A2, CP and FTL, are involved in mitochondrial function, lipid metabolism, and autophagy [ 2 Levi S. Finazzi D. Neurodegeneration with brain iron accumulation: update on pathogenic mechanisms. Front. Pharmacol. 2014; 5: 99 Crossref PubMed Scopus (121) Google Scholar , 3 Gagliardi M. Annesi G. Lesca G. et al. C19orf12 gene mutations in patients with neurodegeneration with brain iron accumulation. Park. Relat. Disord. 2015; 21: 813-816 Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar , 4 Valentino P. Annesi G. Cirò Candiano I.C. et al. Genetic heterogeneity in patients with pantothenate kinase-associated neurodegeneration and classic magnetic resonance imaging eye-of-the-tiger pattern. Mov. Disord. 2006; 21: 252-254 Crossref PubMed Scopus (20) Google Scholar ]. Recently, the COASY gene was identified by Exome sequencing in two subjects with clinical and MRI features typical of NBIA [ [5] Dusi S. Valletta L. Haack T.B. et al. Exome sequence reveals mutations in CoA synthase as a cause of neurodegeneration with brain iron accumulation. Am. J. Hum. Genet. 2014; 94: 11-22 Abstract Full Text Full Text PDF PubMed Scopus (134) Google Scholar ]. They displayed a strikingly similar phenotype, with early-onset spastic-dystonic paraparesis with a later appearance of parkinsonian features, cognitive impairment, and pronounced obsessive-compulsive disorder. This phenotype overlaps with other NBIA disorders. Dusi et al. [ [5] Dusi S. Valletta L. Haack T.B. et al. Exome sequence reveals mutations in CoA synthase as a cause of neurodegeneration with brain iron accumulation. Am. J. Hum. Genet. 2014; 94: 11-22 Abstract Full Text Full Text PDF PubMed Scopus (134) Google Scholar ] identified a homozygous missense mutation in gene, coding for CoA synthase. Coenzyme A is a crucial cofactor in all living organisms and it is involved in several enzymatic reactions. It is a key molecule for the metabolism of fatty acids, carbohydrates, amino acids, and ketone bodies. Its biosynthesis proceeds through a pathway conserved from prokaryotes to eukaryotes, involving five enzymatic steps, which utilize pantothenate (vitamin B5), ATP, and cysteine. They also demonstrate that alterations in RNA and protein expression levels of CoA synthase, as CoA amount, in fibroblasts derived from the two clinical cases and in yeast [ [5] Dusi S. Valletta L. Haack T.B. et al. Exome sequence reveals mutations in CoA synthase as a cause of neurodegeneration with brain iron accumulation. Am. J. Hum. Genet. 2014; 94: 11-22 Abstract Full Text Full Text PDF PubMed Scopus (134) Google Scholar ].

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