The First Iranian Case of Mucopolysaccharidosis IIIC: Use of Homozygosity Mapping in a Consanguineous Pedigree

Mucopolysaccharidosis type IIIC (MPSIIIC) is a rare subtype of mucopolysaccharidosis disorder family caused by mutations in heparan-alpha-glucosaminide N-acetyltransferase (HGSNAT) gene. MPSIIIC is subdivided into four subtypes which have overlapping features, and are indistinguishable at clinical level. In populations with high consanguineous marriage rate, homozygosity mapping can be a good choice for finding a disease locus. Herein we report a female patient with a novel mutation in HGSNAT gene in Iranian population. Clinical diagnosis was accomplished based on clinical manifestations, and urine biochemical analysis. Homozygosity mapping was performed using SNP- array technology to narrow down the candidate locus. All coding exons of HGSNAT were scanned by direct DNA sequencing. We found a novel ins/del mutation as c.1357TA>C. This mutation is a frameshift which eventually leads to premature protein truncation. To the best of our knowledge this is the first case report of Sanfilippo type C in Iranian population. This result also supports the applicability of homozygosity mapping to the diagnosis of Sanfilippo subtype.