PMID- 10205262
OWN - NLM
STAT- MEDLINE
DCOM- 19990520
LR  - 20200824
IS  - 0002-9297 (Print)
IS  - 0002-9297 (Linking)
VI  - 64
IP  - 5
DP  - 1999 May
TI  - Analysis of alkaptonuria (AKU) mutations and polymorphisms reveals that the CCC
      sequence motif is a mutational hot spot in the homogentisate 1,2 dioxygenase gene
      (HGO).
PG  - 1316-22
AB  - We recently showed that alkaptonuria (AKU) is caused by loss-of-function
      mutations in the homogentisate 1,2 dioxygenase gene (HGO). Herein we describe
      haplotype and mutational analyses of HGO in seven new AKU pedigrees. These
      analyses identified two novel single-nucleotide polymorphisms (INV4+31A-->G and
      INV11+18A-->G) and six novel AKU mutations (INV1-1G-->A, W60G, Y62C, A122D,
      P230T, and D291E), which further illustrates the remarkable allelic heterogeneity
      found in AKU. Reexamination of all 29 mutations and polymorphisms thus far
      described in HGO shows that these nucleotide changes are not randomly
      distributed; the CCC sequence motif and its inverted complement, GGG, are
      preferentially mutated. These analyses also demonstrated that the nucleotide
      substitutions in HGO do not involve CpG dinucleotides, which illustrates
      important differences between HGO and other genes for the occurrence of mutation 
      at specific short-sequence motifs. Because the CCC sequence motifs comprise a
      significant proportion (34.5%) of all mutated bases that have been observed in
      HGO, we conclude that the CCC triplet is a mutational hot spot in HGO.
FAU - Beltran-Valero de Bernabe, D
AU  - Beltran-Valero de Bernabe D
AD  - Unidad de Patologia. Centro de Investigaciones Biologicas, Consejo Superior de
      Investigaciones Cientificas, Velazquez 144, 28006-Madrid, Spain.
FAU - Jimenez, F J
AU  - Jimenez FJ
FAU - Aquaron, R
AU  - Aquaron R
FAU - Rodriguez de Cordoba, S
AU  - Rodriguez de Cordoba S
LA  - eng
SI  - GENBANK/AF000573
SI  - GENBANK/AF045167
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Hum Genet
JT  - American journal of human genetics
JID - 0370475
RN  - 0 (Genetic Markers)
RN  - 8J337D1HZY (Cytosine)
RN  - EC 1.13.- (Oxygenases)
RN  - EC 1.13.11.- (Dioxygenases)
RN  - EC 1.13.11.5 (Homogentisate 1,2-Dioxygenase)
SB  - IM
MH  - Alkaptonuria/enzymology/*genetics
MH  - Base Sequence/genetics
MH  - *Cytosine
MH  - *Dioxygenases
MH  - Founder Effect
MH  - Genetic Markers/genetics
MH  - Homogentisate 1,2-Dioxygenase
MH  - Humans
MH  - Molecular Sequence Data
MH  - Mutation, Missense/genetics
MH  - Oxygenases/*genetics
MH  - Pedigree
MH  - Point Mutation/*genetics
MH  - Polymorphism, Genetic/*genetics
MH  - Polymorphism, Single-Stranded Conformational
MH  - Sequence Analysis, DNA
PMC - PMC1377867
EDAT- 1999/04/17 02:14
MHDA- 2000/03/21 09:00
CRDT- 1999/04/17 02:14
PHST- 1999/04/17 02:14 [pubmed]
PHST- 2000/03/21 09:00 [medline]
PHST- 1999/04/17 02:14 [entrez]
AID - S0002-9297(07)62276-9 [pii]
AID - 10.1086/302376 [doi]
PST - ppublish
SO  - Am J Hum Genet. 1999 May;64(5):1316-22. doi: 10.1086/302376.