PMID- 10587575
OWN - NLM
STAT- MEDLINE
DCOM- 20000229
LR  - 20190513
IS  - 0964-6906 (Print)
IS  - 0964-6906 (Linking)
VI  - 9
IP  - 1
DP  - 2000 Jan 1
TI  - A frameshift mutation in prominin (mouse)-like 1 causes human retinal
      degeneration.
PG  - 27-34
AB  - The disks of vertebrate photoreceptors are produced by outgrowths of the plasma
      membrane. Hence genes that encode retinal proteins targeted to plasma membrane
      protrusions represent candidates for inherited retinal degenerations. One such
      candidate is the gene encoding human prominin (mouse)-like 1 (PROML1, previously 
      known as AC133 antigen) which belongs to the prominin family of 5-transmembrane
      domain proteins. Murine prominin (prom) shows a strong preference for plasma
      membrane protrusions in a variety of epithelial cells whereas PROML1 is expressed
      in retinoblastoma cell lines and adult retina. In the present study, molecular
      genetic analyses of a pedigree segregating for autosomal recessive retinal
      degeneration indicated that the affected individuals were homozygous for a
      nucleotide 1878 deletion in PROML1. This alteration is predicted to result in a
      frameshift at codon 614 with premature termination of translation. Expression of 
      a similar prom deletion mutant in CHO cells indicated that the truncated protein 
      does not reach the cell surface. Immunocytochemistry revealed that prom is
      concentrated in the plasma membrane evaginations at the base of the outer
      segments of rod photoreceptors. These findings suggest that loss of prominin
      causes retinal degeneration, possibly because of impaired generation of the
      evaginations and/or impaired conversion of the evaginations to disks.
FAU - Maw, M A
AU  - Maw MA
AD  - Biochemistry Department, University of Otago, PO Box 56, Dunedin, New Zealand.
      marion.maw@stonebow.otago.ac.nz
FAU - Corbeil, D
AU  - Corbeil D
FAU - Koch, J
AU  - Koch J
FAU - Hellwig, A
AU  - Hellwig A
FAU - Wilson-Wheeler, J C
AU  - Wilson-Wheeler JC
FAU - Bridges, R J
AU  - Bridges RJ
FAU - Kumaramanickavel, G
AU  - Kumaramanickavel G
FAU - John, S
AU  - John S
FAU - Nancarrow, D
AU  - Nancarrow D
FAU - Roper, K
AU  - Roper K
FAU - Weigmann, A
AU  - Weigmann A
FAU - Huttner, W B
AU  - Huttner WB
FAU - Denton, M J
AU  - Denton MJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (AC133 Antigen)
RN  - 0 (Antigens, CD)
RN  - 0 (Genetic Markers)
RN  - 0 (Glycoproteins)
RN  - 0 (PROM1 protein, human)
RN  - 0 (Peptides)
RN  - 0 (Prom1 protein, mouse)
SB  - IM
MH  - AC133 Antigen
MH  - Animals
MH  - Antigens, CD
MH  - Cell Membrane/metabolism
MH  - Chromosomes, Human, Pair 4
MH  - Consanguinity
MH  - Female
MH  - *Frameshift Mutation
MH  - Gene Expression Regulation
MH  - Genetic Markers
MH  - Glycoproteins/*genetics/immunology/*metabolism
MH  - Humans
MH  - India
MH  - Male
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Pedigree
MH  - Peptides/*genetics/immunology/*metabolism
MH  - Polydactyly/genetics
MH  - Retinal Degeneration/*genetics
MH  - Rod Cell Outer Segment/metabolism
EDAT- 1999/12/10 09:00
MHDA- 2000/03/04 09:00
CRDT- 1999/12/10 09:00
PHST- 1999/12/10 09:00 [pubmed]
PHST- 2000/03/04 09:00 [medline]
PHST- 1999/12/10 09:00 [entrez]
AID - ddd005 [pii]
AID - 10.1093/hmg/9.1.27 [doi]
PST - ppublish
SO  - Hum Mol Genet. 2000 Jan 1;9(1):27-34. doi: 10.1093/hmg/9.1.27.