PMID- 10227395
OWN - NLM
STAT- MEDLINE
DCOM- 19990610
LR  - 20181113
IS  - 0022-2593 (Print)
IS  - 0022-2593 (Linking)
VI  - 36
IP  - 4
DP  - 1999 Apr
TI  - Identification of a single ancestral CYP1B1 mutation in Slovak Gypsies (Roms)
      affected with primary congenital glaucoma.
PG  - 290-4
AB  - Primary congenital glaucoma (PCG) is an autosomal recessive eye disease that
      occurs at an unusually high frequency in the ethnic isolate of Roms (Gypsies) in 
      Slovakia. Recently, we linked the disease in this population to the GLC3A locus
      on 2p21. At this locus, mutations in the cytochrome P4501B1 (CYP1B1) gene have
      been identified as a molecular basis for this condition. Here, we report the
      results of CYP1B1 mutation screening of 43 PCG patients from 26 Slovak Rom
      families. A homozygous G-->A transition at nucleotide 1505 in the highly
      conserved region of exon 3 was detected in all families. This mutation results in
      the E387K substitution, which affects the conserved K helix region of the
      cytochrome P450 molecule. Determination of the CYP1B1 polymorphic background
      showed a common DNA haplotype in all patients, thus indicating that the E387K
      mutation in Roms has originated from a single ancestral mutational event. The
      Slovak Roms represent the first population in which PCG is found to result from a
      single mutation in the CYP1B1 gene, so that a founder effect is the most
      plausible explanation of its increased incidence. An ARMS-PCR assay has been
      developed for fast detection of this mutation, thus allowing direct DNA based
      prenatal diagnosis as well as gene carrier detection in this particular
      population. Screening of 158 healthy Roms identified 17 (10.8%) mutation
      carriers, indicating that the frequency of PCG in this population may be even
      higher than originally estimated.
FAU - Plasilova, M
AU  - Plasilova M
AD  - Department of Molecular Biology, Comenius University, Bratislava, Slovakia.
FAU - Stoilov, I
AU  - Stoilov I
FAU - Sarfarazi, M
AU  - Sarfarazi M
FAU - Kadasi, L
AU  - Kadasi L
FAU - Ferakova, E
AU  - Ferakova E
FAU - Ferak, V
AU  - Ferak V
LA  - eng
GR  - EY-11095/EY/NEI NIH HHS/United States
GR  - M01-RR-06192/RR/NCRR 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  - England
TA  - J Med Genet
JT  - Journal of medical genetics
JID - 2985087R
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
RN  - EC 1.14.14.1 (Aryl Hydrocarbon Hydroxylases)
RN  - EC 1.14.14.1 (CYP1B1 protein, human)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1B1)
SB  - IM
MH  - *Aryl Hydrocarbon Hydroxylases
MH  - Chromosome Mapping
MH  - Cytochrome P-450 CYP1B1
MH  - Cytochrome P-450 Enzyme System/*genetics
MH  - Glaucoma/*congenital/*genetics
MH  - Humans
MH  - Polymorphism, Genetic/genetics
MH  - Polymorphism, Single-Stranded Conformational
MH  - Romania
PMC - PMC1734351
EDAT- 1999/05/05 00:00
MHDA- 1999/05/05 00:01
CRDT- 1999/05/05 00:00
PHST- 1999/05/05 00:00 [pubmed]
PHST- 1999/05/05 00:01 [medline]
PHST- 1999/05/05 00:00 [entrez]
PST - ppublish
SO  - J Med Genet. 1999 Apr;36(4):290-4.