title: Mutation screening of the HGD gene identifies a novel alkaptonuria mutation with significant founder effect and high prevalence.
abstract: Alkaptonuria (AKU) is an autosomal recessive disorder; caused by the mutations in the homogentisate 1, 2-dioxygenase (HGD) gene located on Chromosome 3q13.33. AKU is a rare disorder with an incidence of 1: 250,000 to 1: 1,000,000, but Slovakia and the Dominican Republic have a relatively higher incidence of 1: 19,000. Our study focused on studying the frequency of AKU and identification of HGD gene mutations in nomads. HGD gene sequencing was used to identify the mutations in alkaptonurics. For the past four years, from subjects suspected to be clinically affected, we found 16 positive cases among a randomly selected cohort of 41 Indian nomads (Narikuravar) settled in the specific area of Tamil Nadu, India. HGD gene mutation analysis showed that 11 of these patients carry the same homozygous splicing mutation c.87 + 1G > A; in five cases, this mutation was found to be heterozygous, while the second AKU-causing mutation was not identified in these patients. This result indicates that the founder effect and high degree of consanguineous marriages have contributed to AKU among nomads. Eleven positive samples were homozygous for a novel mutation c.87 + 1G > A, that abolishes an intron 2 donor splice site and most likely causes skipping of exon 2. The prevalence of AKU observed earlier seems to be highly increased in people of nomadic origin.
authors.affiliation: Department of Biotechnology & Genetic Engineering, Bharathidasan University, Tiruchirapalli, Tamil Nadu, India.
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Sakthivel
authors.forename: Andrea
authors.initials: A
authors.lastname: Zatkova
authors.forename: Martina
authors.initials: M
authors.lastname: Nemethova
authors.forename: Milan
authors.initials: M
authors.lastname: Surovy
authors.forename: Ludevit
authors.initials: L
authors.lastname: Kadasi
authors.forename: Madurai P
authors.initials: MP
authors.lastname: Saravanan
mesh_terms: D000474:Alkaptonuria / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D001483:Base Sequence; D002855:Chromatography, Thin Layer; D004252:DNA Mutational Analysis; D005006:Ethnicity / Q000235:genetics*; D018703:Founder Effect; D005808:Genes, Recessive / Q000235:genetics; D005820:Genetic Testing; D050560:Homogentisate 1,2-Dioxygenase / Q000235:genetics*; D006801:Humans; D007194:India / Q000453:epidemiology; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D015995:Prevalence; D016482:Urinalysis / Q000379:methods
chemical_list: D050560:Homogentisate 1,2-Dioxygenase
keywords: Alkaptonuria; founder effect; high prevalence; novel mutation; rare genetic disorder