A Rare Compound Heterozygous NAGLU Gene Mutation in Two Siblings with Mucopolysaccharidosis type Iiib

TL;DR

Two siblings with a rare genetic mutation in the NAGLU gene are found to have Mucopolysaccharidosis type IIIB, highlighting the importance of identifying such mutations for potential gene therapy.

Contribution

The paper reports a rare compound heterozygous mutation in the NAGLU gene in two siblings with Sanfilippo syndrome type B.

Findings

Enzyme assays showed absent N-acetyl-α-glucosaminidase activity in both siblings.

Targeted sequencing identified two specific mutations in the NAGLU gene: c.214_237dup and c.625A>C.

The findings emphasize the importance of precise mutation identification for gene therapy in monogenic disorders.

Abstract

Mucopolysaccharidosis (MPS) type III, or Sanfilippo syndrome, is an autosomal recessive lysosomal storage disorder caused by mutations in genes encoding enzymes responsible for glycosaminoglycan (GAG) degradation. This case report describes two siblings with MPS type IIIB who exhibit a rare compound heterozygous mutation in the NAGLU gene.

A 7-year-old girl and her 4-year-old brother were referred for evaluation due to learning disabilities, aggressiveness, and coarse facial features. Enzyme assay using tandem mass spectrometry on dried blood spots in both siblings revealed absent N-acetyl-α-glucosaminidase activity.

Targeted sequencing confirmed the diagnosis, identifying two heterozygous mutations—an in-frame insertion and a missense mutation—in exon 3 of the NAGLU gene: c.214_237dup (p.Ala72_Gly79dup) and c.625A>C (p.Thr209Pro). This rare genetic finding in two siblings with Sanfilippo syndrome type B underscores the importance of precise mutation identification. Accurate characterization of defective gene variants may provide insights into potential targets for gene therapy in monogenic disorders.

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