Background/aim
Sanfilippo syndrome is an autosomal recessive lysosomal storage disorder caused by the deficiency of α--acetylglucosaminidase (NAGLU). This leads to lysosomal accumulation of heparan and heparan sulfate. The aim of this study was to analyze the gene in an Egyptian family with two family members manifesting a mild Sanfilippo syndrome type B phenotype which includes mild coarse facial features, hearing loss, clear corneas, and heavy eyebrows with synopherous, mild joint stiffness, mild dementia, and gastrointestinal symptoms.
Subjects and methods
A consanguineous Egyptian family with four siblings was studied. They were three girls and a boy aged 9, 7, 3, and 1 (6/12) years, respectively. Measurement of glycosaminoglycans, two-dimensional electrophoresis, and -acetylglucosaminidase activity were performed to all four siblings. Mutation analysis of the gene was performed using PCR followed by Sanger sequencing of the amplified fragments.
Results
Quantitation of glycosaminoglycans and electrophoresis were done and the diagnosis of Sanfilippo syndrome was confirmed by -acetylglucosaminidase enzyme (NAGLU) deficiency. A missense mutation NM_000263.3:c.934 G>A; p.D312N was detected in exon 5 of the gene in a homozygous pattern in the two affected sisters and in heterozygous form in the two carriers' sister and brother.
Conclusion
A rare missense mutation p.D312N was identified in an Egyptian family with Sanfilippo syndrome type B as homozygous in two affected sisters and heterozygous in the carriers' sister and brother. This rare mutation was previously reported only in three families from France, Iran, and Jordan.