+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Molecular analyses of the HGO gene mutations in Turkish alkaptonuria patients suggest that the R58fs mutation originated from Central Asia and was spread throughout Europe and Anatolia by human migrations



Molecular analyses of the HGO gene mutations in Turkish alkaptonuria patients suggest that the R58fs mutation originated from Central Asia and was spread throughout Europe and Anatolia by human migrations



Journal of Inherited Metabolic Disease 26(1): 17-23



Alkaptonuria (AKU) is a rare metabolic disorder of phenylalanine catabolism that is inherited as an autosomal recessive trait. AKU is caused by loss-of-function mutations in the homogentisate 1,2-dioxygenase (HGO) gene. The deficiency of homogentisate 1,2-dioxygenase activity causes homogentisic aciduria, ochronosis and arthritis. We present the first molecular study of the HGO gene in Turkish AKU patients. Seven unrelated AKU families from different regions in Turkey were analysed. Patients in three families were homozygous for the R58fs mutation; another three families were homozygous for the R225H mutation; and one family was homozygous for the G270R mutation. Analysis of nine intragenic HGO polymorphisms showed that the R58fs, R225H and G270R Turkish AKU mutations are associated with specific HGO haplotypes. The comparison with previously reported haplotypes associated with these mutations from other populations revealed that the R225H is a recurrent mutation in Turkey, whereas G270R most likely has a Slovak origin. Most interestingly, these analyses showed that the Turkish R58fs mutation shares an HGO haplotype with the R58fs mutation found in Finland, Slovakia and India, suggesting that R58fs is an old AKU mutation that probably originated in central Asia and spread throughout Europe and Anatolia during human migrations.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 011001129

Download citation: RISBibTeXText

PMID: 12872836

DOI: 10.1023/a:1024063126954


Related references

R58fs mutation in the HGD gene in a family with alkaptonuria in the UAE. Annals of Human Genetics 73(1): 125-130, 2008

Spectrum of mutations in the familial Mediterranean fever gene (MEFV) in Turkish patients of the Central Anatolia region: a comparison of two mutation detection system. Genetics and Molecular Research 12(4): 5152-5159, 2013

Aldolase B mutations in Turkish families from central anatolia. Genetic Counseling 17(4): 457-460, 2006

Aldolase B mutations in Turkish families from central Anatolia. Genetic Counseling 17(4): 457-460, 2006

Identification of mutations in the galactose-1-phosphate uridyltransferase (GALT) gene in 16 Turkish patients with galactosemia, including a novel mutation of F294Y. Mutation in brief no. 235. Online. Human Mutation 13(4): 339, 1999

High frequency of the 425A-->G splice-site mutation and novel mutations of the COL7A1 gene in central Europe: significance for future mutation detection strategies in dystrophic epidermolysis bullosa. British Journal of Dermatology 152(5): 879-886, 2005

Mutation and polymorphism analysis of the human homogentisate 1,2-dioxygenase gene in Alkaptonuria patients. American Journal Of Human Genetics. 62(4): 776-784, Il, 1998

Mutation analysis of the human homogentisate 1,2 dioxygenase gene in American-based alkaptonuria patients. Pediatric Research 51(4 Part 2): 227A, 2002

Mutation analysis of ATP7B gene in Turkish Wilson disease patients: identification of five novel mutations. European Journal of Medical Genetics 56(4): 175-179, 2013

The NT 1311 polymorphism of G6PD: G6PD Mediterranean mutation may have originated independently in Europe and Asia. American Journal of Human Genetics 47(6): 1008-1012, 1990

Mitochondrial genetic variations of an introduced freshwater fish, goldfish Carassius auratus at the frontier between Europe and Asia (western Anatolia, Turkey): proximity to Europe rather than East Asia?. Mitochondrial Dna. Part A Dna Mapping Sequencing and Analysis 27(6): 4008-4014, 2016

Evidence that the Cys282Tyr mutation of the HFE gene originated from a population in Southern Scandinavia and spread with the Vikings. Clinical Genetics 64(1): 36-47, 2003

Three novel mutations of CHD7 gene in two turkish patients with charge syndrome; A double point mutation and an insertion. Balkan Journal of Medical Genetics 18(1): 65-70, 2015

Spectrum of connexin 26 gene mutations in Turkish families with inherited non-syndromic deafness and determination of the GJB2 35delG mutation carrier frequency in Turkish population. European Journal of Human Genetics 9(Suppl. 1): P0936, 2001

Analysis of HGD Gene Mutations in Patients with Alkaptonuria from the United Kingdom: Identification of Novel Mutations. Jimd Reports 24: 3, 2015