Four novel mutations in the N-acetylgalactosamine-6-sulfate sulfatase gene among Egyptian patients with Morquio A disease.
Morquio A disease (Mucopolysaccharidosis IVA, MPS IVA) is an autosomal recessive lysosomal storage disorder caused by deficient activity of the enzyme N-acetylgalactosamine-6-sulfate sulfatase (GALNS) encoded by the GALNS gene. This deficiency leads to a decreased ability to degrade the glycosaminoglycans (GAGs) keratan sulfate and chondroitin 6-sulfate, thereby causing their accumulation within the lysosomes and consequently prominent skeletal and visceral abnormalities. Clinical evaluation and biochemical GALNS enzyme activity determination were carried out for the patients from four unrelated Egyptian families. Mutational analysis was performed to PCR products by sequencing of the 14 exons and exon-intron boundaries of GALNS gene for the 4 patients. Sequence analysis revealed four novel mutations; three nonsense mutations (p.Q12X, p.Q220X, p.Y254X) and one missense mutation, p.D40G. All four patients were offspring of consanguineous marriages and were homozygous for the corresponding mutation. The activity of the GALNS enzyme was below normal reference range in all of them. The p.Q12X and p.Y254X were associated with severe MPS IVA phenotype. Molecular analysis of GALNS gene revealed four novel mutations in four different Morquio A Egyptian patients.
Department of Biochemical Genetics, Division of Human Genetics and Genome Research, National Research Centre, Dokki12311, Cairo, Egypt. Electronic address: efateen@yahoo.com.
Ekram M
EM
Fateen
Department of Biochemistry, Faculty of pharmacy (Girls), Al Azhar University, Cairo, Egypt. Electronic address: hananmoawad@gmail.com.
Hanan Abd
HA
El Mawgoud
Department of Medical Molecular Genetics, Division of Human Genetics and Genome Research, National Research Centre, Dokki12311, Cairo, Egypt. Electronic address: nr.eissa@yahoo.com.
Noura R
NR
Eissa
Department of Biochemical Genetics, Division of Human Genetics and Genome Research, National Research Centre, Dokki12311, Cairo, Egypt. Electronic address: monamahmoud60@yahoo.com.
Mona M
MM
Ibrahim
Department of Clinical Genetics, Division of Human Genetics and Genome Research, National Research Centre, Dokki12311, Cairo, Egypt. Electronic address: drmona_aglan@yahoo.com.
Mona S
MS
Aglan
Department of Medical Molecular Genetics, Division of Human Genetics and Genome Research, National Research Centre, Dokki12311, Cairo, Egypt. Electronic address: mlessawi@yahoo.com.
Mona L
ML
Essawi
D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002811:Chondroitinsulfatases / Q000235:genetics*; D018389:Codon, Nonsense; D003241:Consanguinity; D004252:DNA Mutational Analysis; D004534:Egypt; D005260:Female; D006720:Homozygote; D006801:Humans; D008297:Male; D009085:Mucopolysaccharidosis IV / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D020125:Mutation, Missense
D018389:Codon, Nonsense; D002811:Chondroitinsulfatases; C102295:GALNS protein, human
Egyptian; GALNS; MPS IVA; Morquio; Mucopolysaccharidosis IV A; Mutation