Refined genetic and physical localization of the Wagner disease (WGN1) locus and the genes CRTL1 and CSPG2 to a 2- to 2.5-cM region of chromosome 5q14.3.
Wagner syndrome (WGN1; MIM 143200), an autosomal dominant vitreoretinopathy characterized by chorioretinal atrophy, cataract, and retinal detachment, is linked to 5q14.3. Other vitreoretinopathies without systemic stigmata, including erosive vitreoretinopathy, are also linked to this region and are likely to be allelic. Within the critical region lie genes encoding two extracellular macromolecules, link protein (CRTL1) and versican (CSPG2), which are important in binding hyaluronan, a significant component of the mammalian vitreous gel, and which therefore represent excellent candidates for Wagner syndrome. Genetic mapping presented here in two further families reduces the critical region to approximately 2 cM. Subsequent refinement of the physical map allows ordering of known polymorphic microsatellites and excludes CRTL1 as a likely candidate for the disorder. CSPG2 is shown to lie within the critical region; however, analysis of the complete coding region of the mature peptide reveals no clear evidence that it is the gene underlying WGN1.
Perveen
R
R
University Department of Medical Genetics and Regional Genetic Service, St. Mary's Hospital, Hathersage Road, Manchester, M13 OJH, United Kingdom.
Hart-Holden
N
N
Dixon
M J
MJ
Wiszniewski
W
W
Fryer
A E
AE
Brunner
H G
HG
Pinkners
A J
AJ
van Beersum
S E
SE
Black
G C
GC
D011508:Chondroitin Sulfate Proteoglycans / Q000235:genetics*; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D004247:DNA / Q000235:genetics; D016326:Extracellular Matrix Proteins; D005192:Family Health; D005260:Female; D006239:Haplotypes; D006801:Humans; D037181:Lectins, C-Type; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D010375:Pedigree; D020161:Physical Chromosome Mapping; D018807:Polymorphism, Single-Stranded Conformational; D011506:Proteins / Q000235:genetics*; D011509:Proteoglycans; D012313:RNA / Q000235:genetics; D012164:Retinal Diseases / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053675:Versicans; D014822:Vitreous Body; D000099249:Proteoglycan Link Protein
D011508:Chondroitin Sulfate Proteoglycans; D004247:DNA; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D011506:Proteins; D011509:Proteoglycans; D012313:RNA; D053675:Versicans; D000099249:Proteoglycan Link Protein; C508322:VCAN protein, human