PMID- 10655546
OWN - NLM
STAT- MEDLINE
DCOM- 20000504
LR  - 20220330
IS  - 0964-6906 (Print)
IS  - 0964-6906 (Linking)
VI  - 9
IP  - 3
DP  - 2000 Feb 12
TI  - Multiple CYP1B1 mutations and incomplete penetrance in an inbred population
      segregating primary congenital glaucoma suggest frequent de novo events and a
      dominant modifier locus.
PG  - 367-74
AB  - Primary congenital glaucoma (PCG) is an autosomal recessive disorder associated
      with unknown developmental defect(s) in the anterior chamber. Recently, we
      reported three distinct mutations in CYP1B1, the gene for cytochrome P4501B1, in 
      25 Saudi families segregating PCG. For this report, we analyzed 37 additional
      families and confirmed the initial finding of decreased penetrance. Mutations and
      intragenic single-nucleotide polymorphisms (SNPs) were also analyzed from direct 
      sequencing of all CYP1B1 coding exons. Eight distinct mutations were identified: 
      G61E, R469W and D374N, the most common Saudi mutations, account for 72, 12 and
      7%, respectively, of all the PCG chromosomes. Five additional homozygous
      mutations (two deletions and three missense mutations) were detected, each in a
      single family. Affected individuals from five families had no CYP1B1 coding
      mutations, and each family had a unique SNP profile. The identification of eight 
      distinct mutations in a single gene, on four distinct haplotypes, suggests a
      relatively recent occurrence of multiple mutations in CYP1B1 in Saudi Arabia.
      These data demonstrate decreased penetrance of the PCG phenotype in the Saudi
      population, because 40 apparently unaffected individuals in 22 families have
      mutations and haplotypes identical to their affected siblings. Two individuals
      were subsequently diagnosed with glaucoma and two others had abnormal ocular
      findings that are consistent with milder forms of glaucoma. Analysis of these 22 
      kindreds suggests the presence of a dominant modifier locus that is not linked
      genetically to CYP1B1. Linkage and Southern analyses excluded three candidate
      modifier loci.
FAU - Bejjani, B A
AU  - Bejjani BA
AD  - Departments of Molecular and Human Genetics, Baylor College of Medicine, One
      Baylor Plaza, Houston, TX 77030, USA. bbejjani@bcm.tmc.edu
FAU - Stockton, D W
AU  - Stockton DW
FAU - Lewis, R A
AU  - Lewis RA
FAU - Tomey, K F
AU  - Tomey KF
FAU - Dueker, D K
AU  - Dueker DK
FAU - Jabak, M
AU  - Jabak M
FAU - Astle, W F
AU  - Astle WF
FAU - Lupski, J R
AU  - Lupski JR
LA  - eng
GR  - K23EY00370/EY/NEI NIH HHS/United States
GR  - K23EY00375/EY/NEI NIH HHS/United States
GR  - R01EY11780/EY/NEI 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  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
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
EIN - Hum Mol Genet 2000 Apr 12;9(7):1141
MH  - Amino Acid Sequence
MH  - *Aryl Hydrocarbon Hydroxylases
MH  - Blotting, Southern
MH  - Consanguinity
MH  - Cytochrome P-450 CYP1B1
MH  - Cytochrome P-450 Enzyme System/*genetics
MH  - DNA Mutational Analysis
MH  - Exons
MH  - Female
MH  - Genetic Linkage
MH  - Glaucoma/congenital/*genetics
MH  - Haplotypes
MH  - Humans
MH  - Male
MH  - Molecular Sequence Data
MH  - Pedigree
MH  - Penetrance
MH  - Point Mutation
MH  - Polymorphism, Single Nucleotide
MH  - Sequence Alignment
EDAT- 2000/02/03 09:00
MHDA- 2000/05/08 09:00
CRDT- 2000/02/03 09:00
PHST- 2000/02/03 09:00 [pubmed]
PHST- 2000/05/08 09:00 [medline]
PHST- 2000/02/03 09:00 [entrez]
AID - ddd038 [pii]
AID - 10.1093/hmg/9.3.367 [doi]
PST - ppublish
SO  - Hum Mol Genet. 2000 Feb 12;9(3):367-74. doi: 10.1093/hmg/9.3.367.