PMID- 8096362
OWN - NLM
STAT- MEDLINE
DCOM- 19930423
LR  - 20200824
IS  - 0002-9297 (Print)
IS  - 1537-6605 (Electronic)
IS  - 0002-9297 (Linking)
VI  - 52
IP  - 4
DP  - 1993 Apr
TI  - Association of the widespread A149P hereditary fructose intolerance mutation with 
      newly identified sequence polymorphisms in the aldolase B gene.
PG  - 835-40
AB  - Hereditary fructose intolerance (HFI) is a potentially fatal autosomal recessive 
      disease resulting from the catalytic deficiency of fructose 1-phosphate aldolase 
      (aldolase B) in fructose-metabolizing tissues. The A149P mutation in exon 5 of 
      the aldolase B gene, located on chromosome 9q21.3-q22.2, is widespread and the 
      most common HFI mutation, accounting for 57% of HFI chromosomes. The possible 
      origin of this mutation was studied by linkage to polymorphisms within the 
      aldolase B gene. DNA fragments of the aldolase B gene containing the polymorphic 
      marker loci from HFI patients homozygous for the A149P allele were amplified by 
      PCR. Absolute linkage to a common PvuII RFLP allele was observed in 10 A149P 
      homozygotes. In a more informative study, highly heterozygous polymorphisms were 
      detected by direct sequence determination of a PCR-amplified aldolase B gene 
      fragment. Two two-allele, single-base-pair polymorphisms, themselves in absolute 
      linkage disequilibrium, in intron 8 (C at nucleotide 84 and A at nucleotide 105, 
      or T at 84 and G at 105) of the aldolase B gene were identified. Mendelian 
      segregation of these polymorphisms was confirmed in three families. 
      Allele-specific oligonucleotide (ASO) hybridizations with probes for both 
      sequence polymorphisms showed that 47% of 32 unrelated individuals were 
      heterozygous at these loci; the calculated PIC value was .37. Finally, ASO 
      hybridizations of PCR-amplified DNA from 15 HFI patients homozygous for the A149P 
      allele with probes for these sequence polymorphisms revealed absolute linkage 
      disequilibrium between the A149P mutation and the 84T/105G allele. These results 
      are consistent with a single origin of the A149P allele and subsequent spread by 
      genetic drift.
FAU - Brooks, C C
AU  - Brooks CC
AD  - Department of Biology, Boston University, MA 02215.
FAU - Tolan, D R
AU  - Tolan DR
LA  - eng
GR  - DK-38821/DK/NIDDK NIH HHS/United States
GR  - DK-43521/DK/NIDDK NIH HHS/United States
GR  - GM-08291/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Hum Genet
JT  - American journal of human genetics
JID - 0370475
RN  - 0 (Genetic Markers)
RN  - 0 (Oligonucleotide Probes)
RN  - EC 4.1.2.13 (Fructose-Bisphosphate Aldolase)
SB  - IM
MH  - Autoradiography
MH  - Base Sequence
MH  - Chi-Square Distribution
MH  - Chromosomes, Human, Pair 9
MH  - Cloning, Molecular
MH  - DNA Mutational Analysis
MH  - Electrophoresis, Gel, Pulsed-Field
MH  - Fructose Intolerance/*genetics
MH  - Fructose-Bisphosphate Aldolase/*genetics
MH  - *Gene Frequency
MH  - Genetic Markers
MH  - Humans
MH  - *Linkage Disequilibrium
MH  - Meiosis
MH  - Molecular Sequence Data
MH  - Mutation
MH  - Oligonucleotide Probes
MH  - Pedigree
MH  - Polymerase Chain Reaction
MH  - *Polymorphism, Restriction Fragment Length
PMC - PMC1682077
EDAT- 1993/04/01 00:00
MHDA- 1993/04/01 00:01
PMCR- 1993/10/01
CRDT- 1993/04/01 00:00
PHST- 1993/04/01 00:00 [pubmed]
PHST- 1993/04/01 00:01 [medline]
PHST- 1993/04/01 00:00 [entrez]
PHST- 1993/10/01 00:00 [pmc-release]
PST - ppublish
SO  - Am J Hum Genet. 1993 Apr;52(4):835-40.