Exome Sequencing Identifies a Biallelic GALNS Variant (p.Asp233Asn) Causing Mucopolysaccharidosis Type IVA in a Pakistani Consanguineous Family

Genes (Basel). 2022 Sep 27;13(10):1743. doi: 10.3390/genes13101743.

Abstract

Mucopolysaccharidoses (MPS) type IVA is a lysosomal storage disease that mainly affects the skeletal system and is caused by a deficiency of the enzyme N-acetylgalactosamine-6-sulfatase (GALNS). The condition can mistakenly be diagnosed as a primary skeletal dysplasia such as spondylo-epiphyseal dysplasia, which shares many similar phenotypic features. Here, we utilised whole exome sequencing to make the diagnosis of MPS IVA in a resource poor country. We report for the first time the identification of a biallelic GALNS missense variant (c.697G>A, p.Asp233Asn) in the Pakistani population and highlight the potential contribution that academic institutions can make in rare disease diagnosis in the absence of a developed clinical genetic service.

Keywords: GALNS; Pakistani consanguineous family; homozygous mutation; mucopolysaccharidosis type IVA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylgalactosamine
  • Chondroitinsulfatases* / genetics
  • Consanguinity
  • Exome / genetics
  • Exome Sequencing
  • Humans
  • Mucopolysaccharidosis IV* / diagnosis
  • Mucopolysaccharidosis IV* / genetics
  • Mutation
  • Pakistan

Substances

  • Chondroitinsulfatases
  • Acetylgalactosamine
  • GALNS protein, human

Grants and funding

This research was funded by Women’s and Children’s Health Research Institute (WCHRI) grant MET gene variants cause a childhood development disorder associated with non-healing fractures” (RES0054178), University of Alberta, Canada.