b-Galactosidase Gene Mutations in Patients With Slowly Progressive GM1 Gangliosidosis

• Published in: Journal of child neurology 1997-06, Vol.12 (4), p.242-247
• Main Authors: Kaye, Edward M, Shalish, Christo, Livermore, James, Taylor, Harold A, Stevenson, Roger E, Breakefield, Xandra O
• Format: Article
• Language: English
• ISSN: 0883-0738
• DOI: 10.1177/088307389701200404

Three unrelated North American cases with slowly progressive forms of G sub(M1) gangliosidosis were found to have two unique point mutations and a 9 bp insertion in the coding region of the gene encoding b-galactosidase. Case 1 was noted to have a 9 bp insertion {CAGAATTTT} on one allele between nucleotides 730 and 731 with no other mutations identified in the other allele. In case 2, two point mutations were found: a unique G1A transition at nucleotide 602 causing an Arg1His substitution in codon 201 (mutation R201H); and a previously identified G1T transition at nucleotide 1527 causing a Trp1Cys substitution in codon 509 (mutation W509C), which has been noted in adult and chronic forms of G sub(M1) gangliosidosis. Case 3 had a unique point mutation (A1G transition at nucleotide 797) resulting in a Asn1Ser amino acid substitution in codon 266 (mutation N266S), with no other mutations found in the same or the other allele. Single-strand conformation polymorphism performed on over 100 controls did not demonstrate the presence of the point mutations R201H or N266S. Also, the mutant proteins coded by the two point mutations did not show enzymatic activity in the Cos-1 cell expression system confirming that these mutations are associated with low enzyme activity. ( J Child Neurol 1997; 12:242-247).