PMID- 10508521
OWN - NLM
STAT- MEDLINE
DCOM- 19991019
LR  - 20190523
IS  - 1061-4036 (Print)
IS  - 1061-4036 (Linking)
VI  - 23
IP  - 2
DP  - 1999 Oct
TI  - Mutations in a human homologue of Drosophila crumbs cause retinitis pigmentosa
      (RP12).
PG  - 217-21
AB  - Retinitis pigmentosa (RP) comprises a clinically and genetically heterogeneous
      group of diseases that afflicts approximately 1.5 million people worldwide.
      Affected individuals suffer from a progressive degeneration of the
      photoreceptors, eventually resulting in severe visual impairment. To isolate
      candidate genes for chorioretinal diseases, we cloned cDNAs specifically or
      preferentially expressed in the human retina and the retinal pigment epithelium
      (RPE) through a novel suppression subtractive hybridization (SSH) method. One of 
      these cDNAs (RET3C11) mapped to chromosome 1q31-q32.1, a region harbouring a gene
      involved in a severe form of autosomal recessive RP characterized by a typical
      preservation of the para-arteriolar RPE (RP12; ref. 3). The full-length cDNA
      encodes an extracellular protein with 19 EGF-like domains, 3 laminin A G-like
      domains and a C-type lectin domain. This protein is homologous to the Drosophila 
      melanogaster protein crumbs (CRB), and denoted CRB1 (crumbs homologue 1). In ten 
      unrelated RP patients with preserved para-arteriolar RPE, we identified a
      homozygous AluY insertion disrupting the ORF, five homozygous missense mutations 
      and four compound heterozygous mutations in CRB1. The similarity to CRB suggests 
      a role for CRB1 in cell-cell interaction and possibly in the maintenance of cell 
      polarity in the retina. The distinct RPE abnormalities observed in RP12 patients 
      suggest that CRB1 mutations trigger a novel mechanism of photoreceptor
      degeneration.
FAU - den Hollander, A I
AU  - den Hollander AI
AD  - Department of Human Genetics, University Hospital Nijmegen, Geert Grooteplein 10,
      P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
FAU - ten Brink, J B
AU  - ten Brink JB
FAU - de Kok, Y J
AU  - de Kok YJ
FAU - van Soest, S
AU  - van Soest S
FAU - van den Born, L I
AU  - van den Born LI
FAU - van Driel, M A
AU  - van Driel MA
FAU - van de Pol, D J
AU  - van de Pol DJ
FAU - Payne, A M
AU  - Payne AM
FAU - Bhattacharya, S S
AU  - Bhattacharya SS
FAU - Kellner, U
AU  - Kellner U
FAU - Hoyng, C B
AU  - Hoyng CB
FAU - Westerveld, A
AU  - Westerveld A
FAU - Brunner, H G
AU  - Brunner HG
FAU - Bleeker-Wagemakers, E M
AU  - Bleeker-Wagemakers EM
FAU - Deutman, A F
AU  - Deutman AF
FAU - Heckenlively, J R
AU  - Heckenlively JR
FAU - Cremers, F P
AU  - Cremers FP
FAU - Bergen, A A
AU  - Bergen AA
LA  - eng
SI  - GENBANK/AF154671
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Nat Genet
JT  - Nature genetics
JID - 9216904
RN  - 0 (DNA, Complementary)
RN  - 0 (Drosophila Proteins)
RN  - 0 (Eye Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (crb protein, Drosophila)
SB  - IM
MH  - Alu Elements/genetics
MH  - Amino Acid Sequence
MH  - Amino Acid Substitution
MH  - Animals
MH  - Base Sequence
MH  - Blotting, Northern
MH  - Cell Line
MH  - Chromosome Mapping
MH  - Chromosomes, Human, Pair 1/genetics
MH  - DNA Mutational Analysis
MH  - DNA, Complementary/chemistry/genetics
MH  - *Drosophila Proteins
MH  - Drosophila melanogaster/genetics
MH  - Eye Proteins/*genetics
MH  - Family Health
MH  - Female
MH  - Gene Expression Regulation, Developmental
MH  - Homozygote
MH  - Humans
MH  - Male
MH  - Membrane Proteins/*genetics
MH  - Molecular Sequence Data
MH  - Mutagenesis, Insertional
MH  - Mutation
MH  - Pedigree
MH  - Point Mutation
MH  - Polymorphism, Single-Stranded Conformational
MH  - RNA, Messenger/genetics/metabolism
MH  - Retinitis Pigmentosa/*genetics/pathology
MH  - Sequence Analysis, DNA
MH  - Tissue Distribution
EDAT- 1999/10/03 09:00
MHDA- 2001/03/23 10:01
CRDT- 1999/10/03 09:00
PHST- 1999/10/03 09:00 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/10/03 09:00 [entrez]
AID - 10.1038/13848 [doi]
PST - ppublish
SO  - Nat Genet. 1999 Oct;23(2):217-21. doi: 10.1038/13848.