Characterization of a novel exonic deletion in the GALNS gene causing Morquio A syndrome

Mucopolysaccharidosis IVA or Morquio A syndrome is a rare lysosomal storage disorder caused by N-acetylgalactosamine-6-sulfatase deficiency. A diagnosis can be provided by the identification of reduced N-acetylgalactosamine-6-sulfatase activity as well as detection of compound heterozygous or homozygous pathogenic variants in GALNS. We present a case of two sisters of healthy non-consanguineous parents with a severe classical phenotype of Morquio A syndrome. Both patients were found to carry a novel homozygous deletion of exon 9, which was initially suspected by next generation sequencing (NGS) due to lack of coverage, but could not be confirmed by this methodology. Therefore, an allele specific polymerase chain reaction assay was designed to confirm the exon 9 deletion and determine the precise deletion breakpoints (c.899-397_1003-1862del) for our patients. Recognizing limitations of molecular testing is important to ensure proper diagnosis and subsequent treatment for individuals with Morquio A syndrome.