Ochronotic rheumatism in Algeria: clinical, radiological, biological and molecular studies--a case study of 14 patients in 11 families.

Abstract

OBJECTIVES:

To confirm alkaptonuria and ochronotic arthropathy diagnosis by mutation screening of the homogentisate 1,2-dioxygenase (HGD) gene. Try to establish a genotype-phenotype correlation in the five subjects with a molecular study on HGD gene.

METHODS:

We report 14 alkaptonuria cases (10 men and four women) in 11 Algerian families. Consanguineous matings were evidenced in only three families (F = 1/16). Molecular analysis was performed by sequencing genomic DNA in order to identify the mutations of the HGD gene.

RESULTS:

Alkaptonuria was always confirmed by urinary homogentisic acid determination. Four different mutations of the HGD gene were found: an homozygous missense mutation, Serine189Isoleucine in two sisters with a mild phenotype; an homozygous splice site mutation (IVS1-1G > A) in a man with a severe phenotype (death at 61 years old from renal failure); a silent mutation, Alanine470Alanine at the heterozygous state in a man with a mild phenotype; a 'G' deletion at the position c.819 which causes a frameshift after Gly217(Gly217fs) that runs into a stop codon at c. 850. This mutation is novel and was found in heterozygosis in a woman with a mild phenotype.

CONCLUSIONS:

The two homozygous mutations were associated, respectively, with a severe and a mild phenotype but no genotype-phenotype correlation could be found.

• Authors: Aicha Ladjouze-Rezig, Santiago Rodriguez de Cordoba, Robert Aquaron
• Journal: Joint bone spine (Joint Bone Spine) Vol. 73 Issue 3 Pg. 284-92 (May 2006) ISSN: 1297-319X [Print] France
• PMID: 16085442 (Publication Type: Case Reports, Journal Article)

Chemical References

• DNA
• Homogentisate 1,2-Dioxygenase

Topics

• Adolescent
• Adult
• Aged
• Alkaptonuria (diagnosis, genetics, pathology)
• DNA (analysis, genetics)
• Female
• Genetic Testing
• Genotype
• Homogentisate 1,2-Dioxygenase (genetics)
• Homozygote
• Humans
• Male
• Middle Aged
• Mutation
• Phenotype
• Rheumatic Diseases (diagnosis, genetics, pathology)