Molecular analysis in a GALNS study cohort of 15 Tunisian patients: description of a novel mutation.
BACKGROUND
Mucopolysaccharidosis type IVA (MPS IVA) is an autosomal recessive disease caused by the deficiency of the lysosomal enzyme N-acetylgalactosamine-6-sulfate sulfatase (GALNS). The purpose of this study was to analyze the GALNS mutations and the haplotypes associated.


METHODS
Mutation screening of the GALNS gene was performed by direct sequence analysis using DNA samples from 15 unrelated Tunisian MPS IVA patients. We also analyzed the haplotypes associated with the novel mutation and with the other reported GALNS mutations.


RESULTS
We have identified an unreported missense mutation p.D288G (c.863A > G) in one patient, the most frequently c.120 + 1G > A (IVS1 + 1G > A) mutation in eleven MPS IVA patients and three previously reported mutations p.G66R, p.A85T and p.R386C on the other MPS IVA patients. All the studied patients were homozygous for these identified mutations. Bioinformatics analysis predicted the novel mutation as being probably pathogenic. These findings with the unobserved p.D288G mutation in controls subjects, suggested that it is a disease-causing mutation, which was correlated with the severe phenotype observed in the patients. We have found that the two GALNS unreported and reported mutations, respectively p.D288G and p.R386C, were associated with a common and specific haplotype.


CONCLUSIONS
Our results were in agreement with previous reports from Tunisia, suggesting, on one hand the genotype/phenotype correlations in MPS IVA patients and the other hand the haplotype analyses were useful for determination of mutation origin in Tunisian population.
Laboratory of Biochemistry, F. Hached Hospital, 4000, Sousse, Tunisia.|University of Monastir, 5000, Monastir, Tunisia.
Latifa
L
Chkioua
Laboratory of Biochemistry, F. Hached Hospital, 4000, Sousse, Tunisia.|University of Monastir, 5000, Monastir, Tunisia.
Souhir
S
Khedhiri
Targeted Therapy Team, The Institute of Cancer Research, London, United Kingdom.
Hind
H
Hafsi
Laboratory of Biochemistry, F. Hached Hospital, 4000, Sousse, Tunisia.
Oussama
O
Grissa
Laboratory of pediatrics, La Rabta Hospital, 1007, Tunis, Tunisia.
Hadhami
H
Ben Turkia
Laboratory of Biochemistry, F. Hached Hospital, 4000, Sousse, Tunisia.|University of Monastir, 5000, Monastir, Tunisia.
Abdelhedi
A
Miled
The Auvergne-Loire Regional Branch of the French National Blood System EFS/GIMAP-EA 3064, 42100, Saint Etienne, France.
Sandrine
S
Laradi
Hereditary Metabolic Diseases Service. Center for biology and pathology, Est Hospices Civils, Lyon, 69677, Bron cedex, France.
Roseline
R
Froissart
Department of Biology, Laboratory of Biotechnologies and Valorization of Natural Resources. IBN Zohr University, School of Sciences, BP 8106, Agadir, Morocco. n.alif@uiz.ac.ma.
Najat
N
Alif
D000595:Amino Acid Sequence; D002675:Child, Preschool; D002811:Chondroitinsulfatases / Q000235:genetics*; D015331:Cohort Studies; D019295:Computational Biology; D004252:DNA Mutational Analysis; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D009085:Mucopolysaccharidosis IV / Q000235:genetics*; D009154:Mutation; D020125:Mutation, Missense; D010641:Phenotype; D016415:Sequence Alignment; D014416:Tunisia
D002811:Chondroitinsulfatases; C102295:GALNS protein, human
Bioinformatics analysis; Haplotypes; Mucopolysaccharidosis type IVA; Mutation screening; N-acetylgalactosamine-6-sulfatase