ArticleEuropean journal of human genetics : EJHG2016
Twelve novel HGD gene variants identified in 99 alkaptonuria patients: focus on 'black bone disease' in Italy.
Article in European journal of human genetics : EJHG, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 102 citations in OpenAlex.
- Radiological evolution of spinal disease in alkaptonuria and the effect of nitisinone.RMD open · 2022Trial
- Homogentisate 1,2-dioxygenase (HGD) gene variants, their analysis and genotype-phenotype correlations in the largest cohort of patients with AKU.European journal of human genetics : EJHG · 2019Trial
- Alkaptonuria in two Colombian patients: identification of HGD variants including a novel finding.BMC medical genomics · 2026Article
- Molecular characterization of Alkaptonuria in Brazilian patients.Molecular genetics and metabolism reports · 2026Article
- Atlas of lysine acetylation in the mouse.bioRxiv : the preprint server for biology · 2026Article
- Article
- Combined alkaptonuria and osteoporosis contributing to chronic back pain.Endocrinology, diabetes & metabolism case reports · 2025Article
- First Documented Hip Replacement in a Palestinian Patient with Ochronotic Alkaptonuria Arthropathy: A Case Report.Journal of orthopaedic case reports · 2025Article
- Direct repair of the chronic ochronotic Achilles tendon rupture: a case report.BMC musculoskeletal disorders · 2024Article
- Alkaptonuria.Nature reviews. Disease primers · 2024Review
- Single-Cell Transcriptome Analysis Reveals Development-Specific Networks at Distinct Synchronized Antral Follicle Sizes in Sheep Oocytes.International journal of molecular sciences · 2024Article
- AI-Driven Enhancements in Drug Screening and Optimization.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Predicting the pathogenicity of missense variants based on protein instability to support diagnosis of patients with novel variants of ARSL.Molecular genetics and metabolism reports · 2023Article
- Breakpoints characterisation of the genomic deletions identified by MLPA in alkaptonuria patients.European journal of human genetics : EJHG · 2023Article
- Article
- Using Graph-Based Signatures to Guide Rational Antibody Engineering.Methods in molecular biology (Clifton, N.J.) · 2023Article
- A robust bacterial high-throughput screening system to evaluate single nucleotide polymorphisms of human homogentisate 1,2-dioxygenase in the context of alkaptonuria.Scientific reports · 2022Article
- Systematic evaluation of computational tools to predict the effects of mutations on protein stability in the absence of experimental structures.Briefings in bioinformatics · 2022Article
- Computational Approaches Integrated in a Digital Ecosystem Platform for a Rare Disease.Frontiers in molecular medicine · 2022Review
- HGDiscovery: An online tool providing functional and phenotypic information on novel variants of homogentisate 1,2- dioxigenase.Current research in structural biology · 2022Article
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Authors and funding
34 authors at 19 institutions in 10 countries.
Funding
No grant is acknowledged in the PubMed record.
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 six in patients from Italy (c.742A>G, c.614G>A, c.1057A>C, c.752G>A, c.119A>C, c.926G>T). Thus, the total number of potential AKU-causing variants found in 380 patients reported in the HGD mutation database is now 129. Using mCSM and DUET, computational approaches based on the protein 3D structure, the novel missense variants are predicted to affect the activity of the enzyme by three mechanisms: decrease of stability of individual protomers, disruption of protomer-protomer interactions or modification of residues in the region of the active site. We also present an overview of AKU in Italy, where so far about 60 AKU cases are known and DNA analysis has been reported for 34 of them. In this rather small group, 26 different HGD variants affecting function were described, indicating rather high heterogeneity. Twelve of these variants seem to be specific for Italy.
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