TY - JOUR
T1 - Exome sequence reveals mutations in CoA synthase as a cause of neurodegeneration with brain iron accumulation
AU - Dusi, Sabrina
AU - Valletta, Lorella
AU - Haack, Tobias B.
AU - Tsuchiya, Yugo
AU - Venco, Paola
AU - Pasqualato, Sebastiano
AU - Goffrini, Paola
AU - Tigano, Marco
AU - Demchenko, Nikita
AU - Wieland, Thomas
AU - Schwarzmayr, Thomas
AU - Strom, Tim M.
AU - Invernizzi, Federica
AU - Garavaglia, Barbara
AU - Gregory, Allison
AU - Sanford, Lynn
AU - Hamada, Jeffrey
AU - Bettencourt, Conceição
AU - Houlden, Henry
AU - Chiapparini, Luisa
AU - Zorzi, Giovanna
AU - Kurian, Manju A.
AU - Nardocci, Nardo
AU - Prokisch, Holger
AU - Hayflick, Susan
AU - Gout, Ivan
AU - Tiranti, Valeria
N1 - Funding Information:
We would like to thank Mario Savoiardo and Federica Zibordi for helpful neuroradiological and clinical support and Fabrizio Villa for experimental advice. The financial support of Telethon GGP11088 to V.T. is gratefully acknowledged. This work was supported by TIRCON project of the European Commission’s Seventh Framework Programme (FP7/2007-2013, HEALTH-F2-2011, grant agreement no. 277984). We thank the Cell line and DNA bank of paediatric movement disorders of the Telethon Genetic Biobank Network (project no. GTB07001) and the Bank for the Diagnosis and Research of Movement Disorders (MDB) of the EuroBiobank. The financial support of Mariani Foundation of Milan is gratefully acknowledged. T.B.H. and S.H. were supported by the NBIA Disorders Association. M.A.K. is a Wellcome Trust Intermediate Clinical Fellow. H.H. and C.B. are grateful to the MRC UK (grant number G0802870) and Backman-Strauss Foundation.
PY - 2014/1/2
Y1 - 2014/1/2
N2 - Neurodegeneration with brain iron accumulation (NBIA) comprises a clinically and genetically heterogeneous group of disorders with progressive extrapyramidal signs and neurological deterioration, characterized by iron accumulation in the basal ganglia. Exome sequencing revealed the presence of recessive missense mutations in COASY, encoding coenzyme A (CoA) synthase in one NBIA-affected subject. A second unrelated individual carrying mutations in COASY was identified by Sanger sequence analysis. CoA synthase is a bifunctional enzyme catalyzing the final steps of CoA biosynthesis by coupling phosphopantetheine with ATP to form dephospho-CoA and its subsequent phosphorylation to generate CoA. We demonstrate alterations in RNA and protein expression levels of CoA synthase, as well as CoA amount, in fibroblasts derived from the two clinical cases and in yeast. This is the second inborn error of coenzyme A biosynthesis to be implicated in NBIA.
AB - Neurodegeneration with brain iron accumulation (NBIA) comprises a clinically and genetically heterogeneous group of disorders with progressive extrapyramidal signs and neurological deterioration, characterized by iron accumulation in the basal ganglia. Exome sequencing revealed the presence of recessive missense mutations in COASY, encoding coenzyme A (CoA) synthase in one NBIA-affected subject. A second unrelated individual carrying mutations in COASY was identified by Sanger sequence analysis. CoA synthase is a bifunctional enzyme catalyzing the final steps of CoA biosynthesis by coupling phosphopantetheine with ATP to form dephospho-CoA and its subsequent phosphorylation to generate CoA. We demonstrate alterations in RNA and protein expression levels of CoA synthase, as well as CoA amount, in fibroblasts derived from the two clinical cases and in yeast. This is the second inborn error of coenzyme A biosynthesis to be implicated in NBIA.
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U2 - 10.1016/j.ajhg.2013.11.008
DO - 10.1016/j.ajhg.2013.11.008
M3 - Article
C2 - 24360804
AN - SCOPUS:84891835067
SN - 0002-9297
VL - 94
SP - 11
EP - 22
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 1
ER -