Work

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

Year: 2025

Type: article

Abstract: Background & Objective: 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.Case Presentation: 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.Conclusion: 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.

Source: Iranian journal of pathology

DOI: 10.30699/ijp.2025.2055938.3426

Authors: Laleh Vahedi-Larijani, Maryam Sotudeh Anvari, Alireza Biglari, Maryam Nabati, Hosna Banihashemi, Marzie Mohammadi Kharkeshi

Institutions: Mazandaran University of Medical Sciences, Children's Medical Center, Tehran University of Medical Sciences, Babol University of Medical Sciences

Language: English

Topic: Lysosomal Storage Disorders Research

Subfield: Physiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $182