CRB1 mutation spectrum in inherited retinal dystrophies.
Mutations in the Crumbs homologue 1 (CRB1) gene have been reported in patients with a variety of autosomal recessive retinal dystrophies, including retinitis pigmentosa (RP) with preserved paraarteriolar retinal pigment epithelium (PPRPE), RP with Coats-like exudative vasculopathy, early onset RP without PPRPE, and Leber congenital amaurosis (LCA). We extended our investigations of CRB1 in these retinal dystrophies, and identified nine novel CRB1 sequence variants. In addition, we screened patients with "classic" RP and classic Coats disease (without RP), but no pathologic sequence variants were found in the CRB1 gene. In total, 71 different sequence variants have been identified on 184 CRB1 alleles of patients with retinal dystrophies, including amino acid substitutions, frameshift, nonsense, and splice site mutations, in-frame deletions, and large insertions. Recent studies in two animal models, mouse and Drosophila, and in vivo high-resolution microscopy in patients with LCA, have shed light on the role of CRB1 in the pathogenesis of retinal dystrophies and its function in the photoreceptors. In this article, we provide an overview of the currently known CRB1 sequence variants, predict their effect, and propose a genotype-phenotype correlation model for CRB1 mutations.
den Hollander
Anneke I
AI
Department of Human Genetics, University Medical Center Nijmegen, Nijmegen, The Netherlands. a.denhollander@antrg.umcn.nl
Davis
Jason
J
van der Velde-Visser
Saskia D
SD
Zonneveld
Marijke N
MN
Pierrottet
Chiara O
CO
Koenekoop
Robert K
RK
Kellner
Ulrich
U
van den Born
L Ingeborgh
LI
Heckenlively
John R
JR
Hoyng
Carel B
CB
Handford
Penny A
PA
Roepman
Ronald
R
Cremers
Frans P M
FP
D000595:Amino Acid Sequence; D000818:Animals; D005136:Eye Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D012164:Retinal Diseases / Q000235:genetics* / Q000473:pathology
C448939:CRB1 protein, human; D005136:Eye Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins