Mutation survey in Taiwanese patients with Stickler syndrome

The purpose of this study was to identify gene mutation and phenotype correlations in a cohort of Taiwanese patients with Stickler syndrome.

Patients clinically diagnosed with Stickler syndrome or suspected Stickler syndrome were enrolled. DNA was extracted from venous blood samples. For the targeted next-generation sequencing (NGS) approach, specific primers were designed for all COL2A1, COL11A1, COL11A2, COL9A1, and COL9A2 exons and flanking intron sequences.

Twenty-three patients from 12 families were enrolled in this study. The myopia power in these 23 cases (35 eyes) ranged from -4.625 to -25.625 D, with a median of -10.00 D. Four patients had retinal detachment. Fourteen patients had a cleft palate. These 23 patients and 13 healthy controls were enrolled in the NGS study. Three families had significant single nucleotide variants (SNVs) in COL2A1. The mutation rates in this survey were 25% (3/12 families) and 35% (8/23 cases). The SNV of family #1, located at exon 27, c.1753G >T, p. Gly585Val, was novel and has not yet been reported in the ClinVar database. Families #10 and #11 had the same SNV, located in exon 33, c.2101C >T, p. Arg701X. Both variants were classified as likely pathogenic according to the American College of Medical Genetics and Genomics guidelines.

Genetic mutations in COL2A1 were found in 25% of Taiwanese families with Stickler syndrome. One novel variant was identified using NGS, which expanded the COL2A1 mutation spectrum. Molecular genetic analysis is helpful to confirm the clinical diagnosis of patients with suspected Stickler syndrome.