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

Abstract

Abstract Background/Objective Sanfilippo 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 methods Thirteen 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. Results In 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. Conclusions This 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.