Morquio A syndrome (mucopolysaccharidosis IVA) is an autosomal recessive disorder that results from deficient activity of the enzyme N‐acetylgalactosamine‐6‐sulfatase (GALNS) due to alterations in the
GALNS gene, which causes major skeletal and connective tissue abnormalities and effects on multiple organ systems. The
GALNS alterations associated with Morquio A are numerous and heterogeneous, and new alterations are continuously identified. To aid detection and interpretation of
GALNS alterations, from previously published research, we provide a comprehensive and up‐to‐date listing of 277 unique
GALNS alterations associated with Morquio A identified from 1,091 published GALNS alleles. In agreement with previous findings, most reported
GALNS alterations are missense changes and even the most frequent alterations are relatively uncommon. We found that 48% of patients are assessed as homozygous for a
GALNS alteration, 39% are assessed as heterozygous for two identified
GALNS alterations, and in 13% of patients only one
GALNS alteration is detected. We report here the creation of a locus‐specific database for the
GALNS gene ( http://galns.mutdb.org/ ) that catalogs all reported alterations in
GALNS to date. We highlight the challenges both in alteration detection and genotype–phenotype interpretation caused in part by the heterogeneity of
GALNS alterations and provide recommendations for molecular testing of
GALNS.
相似文献