Identification of a splice-site mutation in the aldolase B gene from an individual with hereditary fructose intolerance.
Hereditary fructose intolerance (HFI) is a potentially fatal autosomal recessive disease of carbohydrate metabolism. HFI patients exhibit a deficiency of fructose 1-phosphate aldolase (aldolase B), the isozyme expressed in tissues that metabolize fructose. The eight protein-coding exons, including splicing signals, of the aldolase B gene from one HFI patient were amplified by PCR. Dot-blot hybridization of the amplified DNA with allele-specific oligonucleotide (ASO) probes revealed a previously described A149P mutation in one allele from the proband. The mutation in the other allele was identified by direct sequencing of the double-stranded PCR-amplified material from the proband. The nucleotide sequence of exon 9 revealed a 7-base deletion/1-base insertion (delta 7 + 1) at the 3' splice site of intron 8 in one allele. This mutation was confirmed by cloning PCR-amplified exon 9 of the proband and determining the sequence of each allele separately. ASO analysis of 18 family members confirmed the Mendelian inheritance of both mutant alleles. The implications of this unique splice-site mutation in HFI are discussed.
Department of Biology, Boston University, MA 02215.
C C
CC
Brooks
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N
Buist
J
J
Tuerck
D R
DR
Tolan
D000293:Adolescent; D001483:Base Sequence; D003854:Deoxyribonucleotides; D005260:Female; D005633:Fructose Intolerance / Q000235:genetics*; D005634:Fructose-Bisphosphate Aldolase / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D012326:RNA Splicing
D003854:Deoxyribonucleotides; D005634:Fructose-Bisphosphate Aldolase