Targeted next-generation sequencing identifies two novel COL2A1 gene mutations in Stickler syndrome with bilateral retinal detachment

Stickler syndrome is a group of inherited connective tissue disorders characterized by distinctive facial and ocular abnormalities, hearing loss and early-onset arthritis. The aim of the present study was to investigate the genetic changes in two Chinese patients with Stickler syndrome, manifested as bilateral retinal detachment and peripheral retinal degeneration. Complete ophthalmic examinations, including best-corrected visual acuity, slit-lamp examination and fundus examination, were performed. Genomic DNA was extracted from leukocytes of the peripheral blood collected from the patients, their unaffected family members and 200 unrelated control subjects from the same population. Next-generation sequencing of established genes associated with ocular disease was performed. A heterozygous collagen type II α1 chain (COL2A1) mutation c.1310G>C (p.R437P) in exon 21 was identified in Family 1 and a heterozygous COL2A1 mutation c.2302-1G>A in intron 34 was identified in Family 2. The functional effects of the mutations were assessed by polymorphism phenotyping (PolyPhen) and sorting intolerant from tolerant (SIFT) analysis. The c.1310G>C mutation was predicted to damage protein structure and function, and the c.2302-1G>A mutation was predicted to result in a splicing defect. The findings of the current study expand the established mutation spectrum of COL2A1, and may facilitate genetic counseling and development of therapeutic strategies for patients with Stickler syndrome.