Novel missense mutation in the GALNS gene in an affected patient with severe form of mucopolysaccharidosis type IVA.
Mucopolysaccharidosis type IVA (MPS IVA), also known as Morquio A, is an autosomal recessive disorder characterized by a deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS), which causes major skeletal and connective tissue abnormalities and affects multiple organ systems. In this study, one MPS IVA patient with a severe form from consanguine large Iranian family has been investigated. To find a mutation, all of the 14 exons and intron-exon junctions of GALNS gene were sequenced. Sequencing results were analyzed using bioinformatic analysis in order to predict probable pathogenic effect of the variant. One novel homozygous missense mutation in exon 5, c.542A>G (p.Y181C), was found in the proband. That was predicted as being probably pathogenic by bioinformatics analysis. Segregation and familial study confirmed this pathogenic mutation. In conclusion, we have identified the novel mutation responsible for MPS IVA in an Iranian patient to assist in the diagnosis, genetic counseling and prenatal diagnosis of the affected families.
Genomic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Dr. Seyedhassani Medical Genetic Center, Yazd, Iran. Electronic address: sayedhassani@yahoo.com.
Seyed Mohammad
SM
Seyedhassani
Genomic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Feyzollah
F
Hashemi-Gorji
Dr. Seyedhassani Medical Genetic Center, Yazd, Iran.
Mahdieh
M
Yavari
Genomic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Dept. of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Reza
R
Mirfakhraie
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D002648:Child; D002811:Chondroitinsulfatases / Q000737:chemistry / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009085:Mucopolysaccharidosis IV / Q000201:enzymology* / Q000235:genetics*; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D011487:Protein Conformation
D002811:Chondroitinsulfatases; C102295:GALNS protein, human
GALNS gene; Mucopolysaccharidosis type IVA; Mutation