Mucopolysaccharidosis IVA within Tunisian patients: Confirmation of the two novel GALNS gene mutations

• Published in: Pathologie biologie (Paris) Vol. 60; no. 3; pp. 190 - 192
• Main Authors: Khedhiri, S., Chkioua, L., Bouzidi, H., Dandana, A., Ferchichi, S., Ben Turkia, H., Miled, A., Laradi, S.
• Format: Journal Article
• Language: English
• Published: Paris Elsevier SAS 01.06.2012; Elsevier
• Subjects: Adult; Base Sequence; Biological and medical sciences; Carbohydrates (enzymatic deficiencies). Glycogenosis; Chondroitinsulfatases - genetics; Confirmation; Digestion enzymatique; DNA Mutational Analysis; Enzymatic digestion; Errors of metabolism; Genetic Association Studies; Humans; Medical sciences; Metabolic diseases; Molecular Sequence Data; MPS IVA; MPS VI A; Mucopolysaccharidosis IV - epidemiology; Mucopolysaccharidosis IV - genetics; Mutation - physiology; Nouvelles mutations; Novel mutations; Patients tunisiens; Polymorphism, Genetic; Polymorphism, Single-Stranded Conformational - physiology; RNA Splice Sites - genetics; Sequencing; SSCP; Séquençage; Tunisia - epidemiology; Tunisian patients; Validation Studies as Topic; Young Adult; Tunisia; Africa; MPS IVA; Digestion enzymatique; Tunisian patients; Séquençage; Novel mutations; Nouvelles mutations; Enzymatic digestion; SSCP; Patients tunisiens; Confirmation; Sequencing; MPS VI A; Human; Diseases of the osteoarticular system; Metabolic diseases; Mucopolysaccharidosis; Digestion; Enzymopathy; Single strand conformation polymorphism; Genetic disease; Gene; Genetics; Carbohydrate; Mutation
• ISSN: 0369-8114; 1768-3114
• DOI: 10.1016/j.patbio.2011.03.001

Mucopolysaccharidosis type IVA or Morquio A disease is an autosomal recessive disease resulting from a deficiency of the lysosomal enzyme N-acetylgalactosamine-6-sulfate-sulfatase, which hydrolyses N-acetylgalactosamine-6-sulfate and galactose-6-sulfate in glycosaminoglycans. Phenotypes in Morquio A disease vary from the classical form with severe bone dysplasia, heart valve involvement, corneal opacity, short trunk dwarfism and a life span of 20 to 30 years, to attenuated forms with normal life span, mild bone involvement and mild visceral organ involvement. Unlike the other forms of mucopolysaccharidoses, Morquio A disease is characterized by normal intelligence. The aims of this study were to determine if the novel GALNS anomalies IVS1+1G-A and G66R identified in Tunisia are mutations or polymorphisms. This study was carried out on six Morquio A patients recruited from many regions of Tunisia. We have used SCCP, sequencing and enzymatic digestion. IVS1+1G-A and G66R were two deleterious mutations and not polymorphisms. Screening of mutations and polymorphisms in GALNS gene provide useful information on genotype/phenotype correlations. It should also facilitate more accurate genetic counselling of newly diagnosed cases and their family members. La mucopolysaccharidose de type IVA ou Morquio A est une maladie récessive qui résulte de la déficience de l’enzyme lysosomale N-acétylgalactosamine-6-sulfate-sulfatase nécessaire pour l’hydrolyse de la N-acétylgalactosamine-6-sulfate et la galactose-6-sulfate des glycosaminoglycanes. Les phénotypes correspondants à la maladie de Morquio A varient de la forme sévère avec des opacités cornéennes, un nanisme et une durée de vie ne dépassant pas 20 à 30ans, à la forme atténuée avec une vie normale. Contrairement aux autres types de mucopolysaccharidoses, la maladie de Morquio A est caractérisée par une intelligence normale. Le but de cette étude est de confirmer l’aspect délétère des nouvelles mutations IVS1+1G-A et G66R identifiées en Tunisie. Six patients Morquio A ont été recrutés de différentes régions de la Tunisie. Nous avons utilisé les techniques SSCP, séquençage et la digestion enzymatique. Les deux mutations IVS1+1G-A et G66R sont délétères et non pas des polymorphismes. Le screening des mutations et des polymorphismes dans le gène GALNS permet d’assurer des informations sur la corrélation génotype/phénotype afin de faciliter le conseil génétique et le diagnostic prénatal chez les familles à risque.