PMID- 10617778
OWN - NLM
STAT- MEDLINE
DCOM- 20000112
LR  - 20071114
IS  - 1090-0535 (Electronic)
IS  - 1090-0535 (Linking)
VI  - 5
DP  - 1999 Dec 30
TI  - 11-cis retinol dehydrogenase mutations as a major cause of the congenital
      night-blindness disorder known as fundus albipunctatus.
PG  - 41
AB  - PURPOSE: Patients with fundus albipunctatus uniformly experience difficulty with 
      vision at night. Their retinas are spotted with characteristic light yellow
      flecks of unknown composition that typically spare the macula. A defect in the
      transport or utilization of visual cycle retinoids is thought to underlie this
      recessive disorder with variable clinical expression. To elucidate the molecular 
      defect we considered the genes for interphotoreceptor retinoid-binding protein
      (RBP3) and 11-cis retinol dehydrogenase (RDH5) as candidates for this disease.
      METHODS: We examined two unrelated families with fundus albipunctatus. The
      diagnosis was determined clinically and RBP3 and RDH5 were analyzed by molecular 
      screening methods and direct genomic sequencing. RESULTS: Each family had two
      affected members with typical fundus albipunctatus. The affected members were
      siblings born to unaffected parents who were seventh cousins in the first family 
      and unrelated in the second family. The probands from both families were
      clinically similar except for the fundus dots that were more extensive in the
      second family to the point of involving the parafoveal region. In the initial
      phase of genetic screening RBP3 defects were ruled-out as the cause of the
      disease in both families. In contrast, RDH5 mutations were found in the affected 
      siblings in both families. The proband in one had a homozygotic Gly238Trp
      missense mutation (GGG -> TGG) involving exon 4 and in the other carried compound
      heterozygotic changes Arg280His (CGC -> CAC) and Ala294Pro (GCC -> CCC) in exon
      5. The disease phenotype was only manifested in family members with two abnormal 
      RDH5 alleles consistent with autosomal recessive inheritance in both pedigrees.
      CONCLUSIONS: These findings strongly implicate defects of RDH5 as the cause of
      fundus albipunctatus and point to a heterogeneity of RDH5 mutations in this form 
      of congenital stationary night blindness with variable expressivity.
FAU - Gonzalez-Fernandez, F
AU  - Gonzalez-Fernandez F
AD  - Departments of Ophthalmology and Pathology (Neuropathology), Graduate Program in 
      Neuroscience, University of Virginia Health Sciences Center Charlottesville, VA
      22908, USA. fg2z@Virginia.edu
FAU - Kurz, D
AU  - Kurz D
FAU - Bao, Y
AU  - Bao Y
FAU - Newman, S
AU  - Newman S
FAU - Conway, B P
AU  - Conway BP
FAU - Young, J E
AU  - Young JE
FAU - Han, D P
AU  - Han DP
FAU - Khani, S C
AU  - Khani SC
LA  - eng
GR  - EY01931/EY/NEI NIH HHS/United States
GR  - EY09412/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.
DEP - 19991230
PL  - United States
TA  - Mol Vis
JT  - Molecular vision
JID - 9605351
RN  - 0 (Eye Proteins)
RN  - 0 (Retinol-Binding Proteins)
RN  - 0 (interstitial retinol-binding protein)
RN  - 9007-49-2 (DNA)
RN  - EC 1.1.- (Alcohol Oxidoreductases)
RN  - EC 1.1.1.105 (retinol dehydrogenase)
SB  - IM
MH  - Adult
MH  - Alcohol Oxidoreductases/*genetics
MH  - Base Sequence
MH  - DNA/chemistry
MH  - Eye Diseases, Hereditary/*genetics
MH  - *Eye Proteins
MH  - Female
MH  - Humans
MH  - Male
MH  - Mutation
MH  - Night Blindness/congenital/*genetics
MH  - Pedigree
MH  - Polymerase Chain Reaction
MH  - Polymorphism, Single-Stranded Conformational
MH  - Retinal Diseases/congenital/*genetics
MH  - Retinol-Binding Proteins/*genetics
EDAT- 2000/01/05 00:00
MHDA- 2000/01/05 00:01
CRDT- 2000/01/05 00:00
PHST- 2000/01/05 00:00 [pubmed]
PHST- 2000/01/05 00:01 [medline]
PHST- 2000/01/05 00:00 [entrez]
PST - epublish
SO  - Mol Vis. 1999 Dec 30;5:41.