Identification of Three Novel Homozygous NAGLU Mutations in Egyptian Patients with Sanfilippo Syndrome B

Abstract

Background/ObjectiveSanfilippo syndrome type B is an autosomal recessive lysosomal storage disorder caused by deficiencies of the lysosomal enzyme alpha-N-acetylglucosaminidase (NAGLU). This study is aimed to explore and analyze the genetics of NAGLU gene in a cohort of Egyptian patients with Sanfilippo syndrome type B. Patients and methodsThirteen children were diagnosed with a deficiency in the enzyme alpha-N-acetylglucosaminidase (NAGLU) and presented with other supportive clinical symptoms including aggressive behavior and hyperactivity along with severe mental retardation. The NAGLU gene analysis was performed using PCR followed by Sanger's sequencing of the amplified fragments. ResultsIn this study, 10 different mutations were identified, including 3 novel mutations (K255Rfs*18, E153Rfs*39, and Q350*) and 7 previously reported ones (Y558*, L550P, R297*, R482W, G79C, Y140C, and W268R). The majority of the 10 mutations were homozygous mutations (8/10) (80%), one compound heterozygous for Y140C/W268R (10%) and one heterozygous mutation R482W/? (10%), the second hit was not identified. The most common mutation was L550P (6/25) (24%), followed by Y558* (4/25) (16%) and then R482W (3/25) (12%). Fifteen of the mutant alleles (15/25) (60%) were located in exon 6 of the NAGLU gene, suggesting that exon 6 is a mutational hotspot in Egyptian patients. ConclusionsThis is the first study of NAGLU gene analysis in Egyptian patients with Sanfilippo syndrome type B that involved 3 novel homozygote mutations. This study could have valuable implications in genetic counseling and further clinical genetic studies of MPS IIIB syndrome.