Journal article

Twelve novel HGD gene variants identified in 99 alkaptonuria patients: focus on 'black bone disease' in Italy

Martina Nemethova, Jan Radvanszky, Ludevit Kadasi, David B Ascher, Douglas EV Pires, Tom L Blundell, Berardino Porfirio, Alessandro Mannoni, Annalisa Santucci, Lia Milucci, Silvia Sestini, Gianfranco Biolcati, Fiammetta Sorge, Caterina Aurizi, Robert Aquaron, Mohammed Alsbou, Charles Marques Lourenco, Kanakasabapathi Ramadevi, Lakshminarayan R Ranganath, James A Gallagher Show all

EUROPEAN JOURNAL OF HUMAN GENETICS | NATURE PUBLISHING GROUP | Published : 2016

Abstract

Alkaptonuria (AKU) is an autosomal recessive disorder caused by mutations in homogentisate-1,2-dioxygenase (HGD) gene leading to the deficiency of HGD enzyme activity. The DevelopAKUre project is underway to test nitisinone as a specific treatment to counteract this derangement of the phenylalanine-tyrosine catabolic pathway. We analysed DNA of 40 AKU patients enrolled for SONIA1, the first study in DevelopAKUre, and of 59 other AKU patients sent to our laboratory for molecular diagnostics. We identified 12 novel DNA variants: one was identified in patients from Brazil (c.557T>A), Slovakia (c.500C>T) and France (c.440T>C), three in patients from India (c.469+6T>C, c.650-85A>G, c.158G>A), and..

View full abstract

Grants

Awarded by European Commission Seventh Framework Programme


Awarded by ERDF (the project 'Creating a Competitive Centre for research and development in the field of molecular medicine')


Awarded by Slovak National Agency VEGA


Awarded by NHMRC CJ Martin Fellowship


Funding Acknowledgements

DNA analysis of SONIA1 samples was supported by the European Commission Seventh Framework Programme funding granted in 2012 (DevelopAKUre, project number: 304985). Analysis of remaining patients was performed thanks to the Research & Developmental Operational Programme funded by the ERDF (the project 'Creating a Competitive Centre for research and development in the field of molecular medicine' ITMS 26240220071), and the Slovak National Agency VEGA (grant No. 2/0027/12). DBA is supported by a NHMRC CJ Martin Fellowship (GNT1072476). DEVP is supported by the Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), Brazil.