Two new human {beta}-galactosidase gene mutations in American patients with slowly progressive G{sub M1} gangliosidosis
- Massachusetts General Hospital, Boston, MA (United States)
- Tufts Univ. School of Medicine, Boston, MA (United States); and others
Two cases with slowly progressive forms of G{sub M1} gangliosidosis were each found to have a novel mutation for the {beta}-galactosidase gene. AS (died at 4 yr) began with symptoms at 8 months ({beta}-galactosidase activity 10% normal) and HS (59 yr) developed dystronic hand movements at age 3 yr ({beta}-galactosidase activity < 2% of normal controls). The entire 2.4 coding region was sequenced in both directions for each patient using RT-PCR. First strand cDNA was synthesized from fibroblast RNA and double stranded PCR fragments spanning the coding region were made with oligonucleotide primers. Sequencing was performed using asymmetric PCR products made from each double stranded product. Case AS was found to have a nine base-pair insertion [CAGAATTTT] on one allele beginning at nucleotide position 730, which did not result in a frameshift and is predicted to cause the insertion of three amino acids (Glu-Phe-Ser) between amino acids 44-45. No other mutations in the coding region were identified on this or the other allele in this individual. Case HS had a unique point mutation identified in one allele. This mutation was an A{r_arrow}G transition at nucleotide 797 which results in a Asn{r_arrow}Ser amino acid substitution in codon 266 (mutation N266S) with no other mutations found in the expressed RNA sequences. SSCP was performed on a 200 bp region surrounding codon 266 using genomic DNA from over 50 controls to look for changes in nucleotide sequence. Only case HS demonstrated a shift indicating that the base pair change did not represent a normal polymorphism.
- OSTI ID:
- 134320
- Report Number(s):
- CONF-941009-; ISSN 0002-9297; TRN: 95:005313-1053
- Journal Information:
- American Journal of Human Genetics, Vol. 55, Issue Suppl.3; Conference: 44. annual meeting of the American Society of Human Genetics, Montreal (Canada), 18-22 Oct 1994; Other Information: PBD: Sep 1994
- Country of Publication:
- United States
- Language:
- English
Similar Records
Mutations in acid [beta]-galactosidase cause GM[sub 1]-gangliosidosis in American patients
A mutation in arylsulfatase B gene causes mucopolysuccharidosis VI in rats