A novel mutation in Intron 11 of the COL2A1 Gene in a patient with Type I Stickler Syndrome

Abstract

Abstract: : Purpose: To present one case of a novel mutation in intron 11 of the COL2A1 gene in a patient with type I Stickler syndrome. Methods: 1) Case report; 2) Genetic analysis: Whole blood was drawn from the patient’s father and genomic DNA extracted. The 54 exons and exon/intron boundaries of the COL2A1 gene were amplified using oligonucleotide primers and PCR. The PCR products were analyzed using conformation sensitive gel electrophoresis (CSGE), a technique that detects single–base changes by increasing differential migration of homoduplexes and mutation–induced heteroduplexes. PCR products generating heteroduplexes were then sequenced. Results: An 8 year old boy with cleft palate who presented with floaters in his right eye was discovered to have bilateral vitreous abnormalities and a family history of rhegmatogenous retinal detachment, myopia, bony abnormalities, and hearing loss. Best corrected visual acuity was 20/20 OU. Ophthalmoscopy revealed retrolental vitreous membranes, optically empty vitreous cavity, thickened posterior hyaloid membrane and retinal tears OU, which were treated with cryopexy. Subsequent examinations revealed progressing myopia and more retinal tears OU, treated again with cryopexy. CSGE analysis detected a sequence variation in the fragment containing intron 11, and subsequent sequencing showed a G to T substitution in the 5+ position. The patient’s father was heterozygous for the mutation, and genetic analysis of other family members was recommended. Conclusions: The genetic analysis performed in this case brings to light a novel mutation in intron 11 of COL2A1, which encodes type II collagen. The mutation may abolish the intron donor splice site or activate a cryptic splice site, leading to aberrant mRNA splicing and a frameshift that creates a premature termination codon. The subsequent abnormality in collagen homotrimer assembly may put the patient at risk for vitreous traction and retinal detachment. This case illustrates the diversity of genetic mutations found in Stickler syndrome.

Keywords: retinal detachment • genetics • vitreous