Mucopolysaccharidosis IVA (MPS IVA; Morquio A disease) is an autosomal recessive disorder caused by a deficiency of the lysosomal N-acetylgalactosamine-6-sulfate sulfatase (GALNS; E.C.3.1.6.4; OMIM# 253000). GALNS is one of the sulfatases required to degrade glycosaminoglycans (GAGs), keratan sulfate (KS), and chondroitin-6-sulfate (C6S). GALNS deficiency results in lysosomal storage disease. As in other mucopolysaccharidoses, MPS IVA patients have a broad spectrum of clinical severity. Phenotypes vary from the classical form with severe bone dysplasia (spondyloepiphyseal dysplasia), short trunk dwarfism, coxa valga, odontoid hypoplasia, corneal opacity, and a life span of 20–30 years, to a milder (attenuated) form. The patients with a milder form may have a normal quality of life and mild bone and visceral organ involvement. The broad spectrum of clinical phenotypes seen in MPS IVA is presumed to be generated by multiple different GALNS mutations. Investigations of the molecular nature of MPS IVA have been facilitated by purifying the enzyme, and by isolating and characterising both the GALNS gene and the full-length cDNA encoding the human GALNS protein.^1–3 The cDNA contains an open reading frame of 1566 bp which encodes a 522-residue polypeptide. The gene spans approximately 50 kb, and contains 14 exons (GDB Accession ID: 129085).

Molecular analyses of over 100 MPS IVA patients with diverse ethnic or geographic origins (Australian, British, Colombian, Finnish, German, Irish, Japanese, and Turkish) have been reported.^4–11 To date, around 90 different mutations responsible for various phenotypes have been identified, documenting the allelic heterogeneity in the GALNS gene, which correlates with the clinical variability within MPS IVA. Most of the known mutations (85–95%) in the GALNS gene have been detected by using PCR of genomic DNA for each exon (14 amplicons) and single-strand conformation polymorphism (SSCP),^6–12 a reliable screening method.

The variety (missense or nonsense), frequency, and …