Chapter title |
Identification of 11 Novel Homogentisate 1,2 Dioxygenase Variants in Alkaptonuria Patients and Establishment of a Novel LOVD-Based HGD Mutation Database.
|
---|---|
Chapter number | 68 |
Book title |
JIMD Reports - Case and Research Reports, 2012/1
|
Published in |
JIMD Reports, October 2011
|
DOI | 10.1007/8904_2011_68 |
Pubmed ID | |
Book ISBNs |
978-3-64-225751-3, 978-3-64-225752-0
|
Authors |
Zatkova A, Sedlackova T, Radvansky J, Polakova H, Nemethova M, Aquaron R, Dursun I, Usher JL, Kadasi L, Andrea Zatkova, Tatiana Sedlackova, Jan Radvansky, Helena Polakova, Martina Nemethova, Robert Aquaron, Ismail Dursun, Jeannette L. Usher, Ludevit Kadasi |
Abstract |
Enzymatic loss in alkaptonuria (AKU), an autosomal recessive disorder, is caused by mutations in the homogentisate 1,2 dioxygenase (HGD) gene, which decrease or completely inactivate the function of the HGD protein to metabolize homogentisic acid (HGA). AKU shows a very low prevalence (1:100,000-250,000) in most ethnic groups, but there are countries with much higher incidence, such as Slovakia and the Dominican Republic. In this work, we report 11 novel HGD mutations identified during analysis of 36 AKU patients and 41 family members from 27 families originating from 9 different countries, mainly from Slovakia and France. In Slovak patients, we identified two additional mutations, thus a total number of HGD mutations identified in this small country is 12. In order to record AKU-causing mutations and variants of the HGD gene, we have created a HGD mutation database that is open for future submissions and is available online ( http://hgddatabase.cvtisr.sk/ ). It is founded on the Leiden Open (source) Variation Database (LOVD) system and includes data from the original AKU database ( http://www.alkaptonuria.cib.csic.es ) and also all so far reported variants and AKU patients. Where available, HGD-haplotypes associated with the mutations are also presented. Currently, this database contains 148 unique variants, of which 115 are reported pathogenic mutations. It provides a valuable tool for information exchange in AKU research and care fields and certainly presents a useful data source for genotype-phenotype correlations and also for future clinical trials. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
Netherlands | 1 | 100% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 26 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Lecturer | 3 | 12% |
Student > Master | 3 | 12% |
Researcher | 2 | 8% |
Student > Bachelor | 2 | 8% |
Student > Ph. D. Student | 2 | 8% |
Other | 2 | 8% |
Unknown | 12 | 46% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 5 | 19% |
Biochemistry, Genetics and Molecular Biology | 5 | 19% |
Agricultural and Biological Sciences | 2 | 8% |
Pharmacology, Toxicology and Pharmaceutical Science | 1 | 4% |
Neuroscience | 1 | 4% |
Other | 0 | 0% |
Unknown | 12 | 46% |