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Joint Bone Spine
Volume 73, n° 3
pages 284-292 (mai 2006)
Doi : 10.1016/j.jbspin.2005.03.010
Received : 21 July 2004 ;  accepted : 30 Mars 2005
Ochronotic rheumatism in Algeria: clinical, radiological, biological and molecular studies—a case study of 14 patients in 11 families
 

Aicha Ladjouze-Rezig a , Santiago Rodriguez de Cordoba b, Robert Aquaron c,
a Rheumatology Department, Ben Aknoun Hospital, Route des deux bassins, 16300 Algiers, Algeria 
b Departamento de Immunologia, Centro de Investigaciones Biologicas, Consejo Superior de Investigaciones Biologicas, Madrid, Spain 
c Laboratoire de Biochimie et Biologie Moléculaire, Faculté de Médecine, Université de la Méditerranée, 27, boulevard Jean Moulin, 13385 Marseille cedex 5, France 

*Corresponding author.
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.

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Keywords : Alkaptonuria, Homogentisate 1,2-dioxygenase, Homogentisic acid, Ochronosis, Ochronotic arthropathy




© 2005  Elsevier SAS. All Rights Reserved.