Structural and functional study of K453E mutant protective protein/cathepsin A causing the late infantile form of galactosialidosis

The most heterogeneous pool of CTSA mutations has been found in patients with the severe, early infantile form of GS, although some recurrent mutations point to a founder effect in specific ethnic groups.

“As foreseeable, the most heterogeneous pool of CTSA mutations have been found in patients with the severe, early infantile form of GS, although some recurrent mutations seem to point to a founder effect in specific ethnic groups 20–23.”

There is a strong correlation between the type and combination of amino acid substitutions and the clinical outcome in GS.

“In general, we can assert that there is a strong correlation between the type and combination of amino acid substitutions and the clinical outcome.”

Late infantile GS is characterized by two recurrent missense mutations, Phe458Val and Tyr267Asn, that appear pathognomonic for this clinical phenotype.

“Instead, the group of patients with the late infantile form of the disease is characterized by two recurrent, missense mutations, resulting in two amino acid substitutions, Phe458Val and Tyr267Asn, that appear to be pathognomonic for this clinical phenotype.”

The majority of CTSA mutations reported in the literature have been identified in Japanese patients, who share a common single base substitution at the donor splice site of intron 7 causing skipping of exon 7 (SpDEx7), and this mutation apparently segregates with the juvenile/adult type.

“By far, the majority of CTSA mutations reported in the literature have been identified in Japanese patients 8,20,21.”