Autosomal dominant rhegmatogenous retinal detachment associated with an Arg453Ter mutation in the COL2A1 gene.
OBJECTIVE
To investigate the clinical features and molecular causes of autosomal dominant rhegmatogenous retinal detachment (RRD) in two large families.


METHODS
Clinical examination and linkage analysis of both families using markers flanking the COL2A1 gene associated with Stickler syndrome type 1, the loci for Wagner disease/erosive vitreoretinopathy (5q14.3), high myopia (18p11.31 and 12q21-q23), and nonsyndromic congenital retinal nonattachment (10q21).


RESULTS
Fifteen individuals from family A and 12 individuals from family B showed RRD or retinal tears with minimal (family A) or no (family B) systemic characteristics of Stickler syndrome and no ocular features of Wagner disease or erosive vitreoretinopathy. The RRD cosegregated fully with a chromosomal region harboring the COL2A1 gene with maximum lod scores of 6.09 (family A) and 4.97 (family B). In family B, an Arg453Ter mutation was identified in exon 30 of the COL2A1 gene, that was previously described in a patient with classic Stickler syndrome. In family A, DNA sequence analysis revealed no mutation in the coding region and at the splice sites of the COL2A1 gene.


CONCLUSIONS
In two large families with RRD, linkage was found at the COL2A1 locus. In one of these families an Arg453Ter mutation was identified, which is surprising, because all predominantly ocular Stickler syndrome cases until now have been associated with protein-truncating mutations in exon 2, an exon subject to alternative splicing. In contrast, the Arg453Ter mutation and other protein-truncating mutations in the helical domain of COL2A1 have been associated until now with classic Stickler syndrome.
Go
Sioe Lie
SL
Department of Ophthalmology, University Medical Centre Nijmegen, Nijmegen, The Netherlands.
Maugeri
Alessandra
A
Mulder
Jef J S
JJ
van Driel
Marc A
MA
Cremers
Frans P M
FP
Hoyng
Carel B
CB
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D018388:Codon, Terminator / Q000235:genetics; D024043:Collagen Type II / Q000235:genetics*; D003240:Connective Tissue Diseases / Q000235:genetics; D004252:DNA Mutational Analysis; D005128:Eye Diseases / Q000235:genetics; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D012162:Retinal Degeneration / Q000235:genetics; D012163:Retinal Detachment / Q000235:genetics*; D012167:Retinal Perforations / Q000235:genetics; D013577:Syndrome; D014822:Vitreous Body / Q000473:pathology
C499177:COL2A1 protein, human; D018388:Codon, Terminator; D024043:Collagen Type II