PMID- 10391219
OWN - NLM
STAT- MEDLINE
DCOM- 19990719
LR  - 20101118
IS  - 1061-4036 (Print)
IS  - 1061-4036 (Linking)
VI  - 22
IP  - 3
DP  - 1999 Jul
TI  - Mutations in the gene encoding 3 beta-hydroxysteroid-delta 8, delta 7-isomerase
      cause X-linked dominant Conradi-Hunermann syndrome.
PG  - 291-4
AB  - X-linked dominant Conradi-Hunermann syndrome (CDPX2; MIM 302960) is one of a
      group of disorders with aberrant punctate calcification in cartilage, or
      chondrodysplasia punctata (CDP). This is most prominent around the vertebral
      column, pelvis and long bones in CPDX2. Additionally, CDPX2 patients may have
      asymmetric rhizomesomelia, sectorial cataracts, patchy alopecia, ichthyosis and
      atrophoderma. The phenotype in CDPX2 females ranges from stillborn to mildly
      affected individuals identified in adulthood. CDPX2 is presumed lethal in males, 
      although a few affected males have been reported. We found increased
      8(9)-cholestenol and 8-dehydrocholesterol in tissue samples from seven female
      probands with CDPX2 (ref. 4). This pattern of accumulated cholesterol
      intermediates suggested a deficiency of
      3beta-hydroxysteroid-delta8,delta7-isomerase (sterol-delta8-isomerase), which
      catalyses an intermediate step in the conversion of lanosterol to cholesterol. A 
      candidate gene encoding a sterol-delta8-isomerase (EBP) has been identified and
      mapped to Xp11.22-p11.23 (refs 5,6). Using SSCP analysis and sequencing of
      genomic DNA, we found EBP mutations in all probands. We confirmed the functional 
      significance of two missense alleles by expressing them in a
      sterol-delta8-isomerase-deficient yeast strain. Our results indicate that defects
      in sterol-delta8-isomerase cause CDPX2 and suggest a role for sterols in bone
      development.
FAU - Braverman, N
AU  - Braverman N
AD  - Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore,
      Maryland 21205, USA.
FAU - Lin, P
AU  - Lin P
FAU - Moebius, F F
AU  - Moebius FF
FAU - Obie, C
AU  - Obie C
FAU - Moser, A
AU  - Moser A
FAU - Glossmann, H
AU  - Glossmann H
FAU - Wilcox, W R
AU  - Wilcox WR
FAU - Rimoin, D L
AU  - Rimoin DL
FAU - Smith, M
AU  - Smith M
FAU - Kratz, L
AU  - Kratz L
FAU - Kelley, R I
AU  - Kelley RI
FAU - Valle, D
AU  - Valle D
LA  - eng
SI  - GENBANK/AF030357
SI  - GENBANK/X97755
SI  - GENBANK/Z37985
SI  - GENBANK/Z37986
GR  - P01HD10981/HD/NICHD NIH HHS/United States
GR  - RR00052/RR/NCRR NIH HHS/United States
GR  - RR00722/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  - United States
TA  - Nat Genet
JT  - Nature genetics
JID - 9216904
RN  - 0 (Carrier Proteins)
RN  - 0 (DNA Primers)
RN  - 9007-49-2 (DNA)
RN  - EC 5.3.3.- (Steroid Isomerases)
RN  - EC 5.3.3.- (delta(8)-delta(7)-sterol isomerase)
RN  - EC 5.3.3.5 (EBP protein, human)
SB  - IM
MH  - Adolescent
MH  - Base Sequence
MH  - Carrier Proteins/genetics
MH  - Child
MH  - Chondrodysplasia Punctata/*enzymology/*genetics
MH  - DNA/genetics
MH  - DNA Primers/genetics
MH  - Female
MH  - Genetic Linkage
MH  - Humans
MH  - Infant, Newborn
MH  - Molecular Sequence Data
MH  - *Mutation
MH  - Pregnancy
MH  - Steroid Isomerases/*genetics
MH  - X Chromosome/*genetics
EDAT- 1999/07/03 10:00
MHDA- 2001/03/23 10:01
CRDT- 1999/07/03 10:00
PHST- 1999/07/03 10:00 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/07/03 10:00 [entrez]
AID - 10.1038/10357 [doi]
PST - ppublish
SO  - Nat Genet. 1999 Jul;22(3):291-4. doi: 10.1038/10357.