Purpose:
Stickler syndrome is associated with the development of rhegmatogenous retinal detachment (RRD), and often presents with ocular, auditory, skeletal, and orofacial abnormalities. Molecular analysis has proven effective in diagnosis, confirmation and classification of the disease. We aimed to describe the utility of next-generation sequencing (NGS) in genetic analysis of four Indian families with suspected Stickler syndrome.
Methods:
The index cases presented with retinal detachment with family history. Genetic analysis in the index case was performed by next-generation sequencing of inherited retinal degeneration genes, and validated by Sanger sequencing followed by co-segregation analysis in the other family members.
Results:
Twenty patients were included for the genetic analysis (15 males and 5 females from four families). Clinical details were available for 15 patients (30 eyes). Fourteen eyes (11 patients) developed RRD. In the 16 eyes without RRD, 8 underwent barrage laser to lattice degeneration and 8 were under observation. Disease segregating heterozygous mutations with pathogenic/likely pathogenic effect was identified in
COL2A1
(c.4318-1G>A, c.141G>A, c.1221+1G>A for 3 families) and
COL11A1
(c.1737+1 G>A for 1 family) gene. In addition to the mutation in the
COL2A1
gene, a pathogenic heterozygous variant associated with risk for arrhythmogenic right ventricular cardiomyopathy (ARVC) was identified in one member.
Conclusion:
NGS testing confirmed the presence of the causative gene for Stickler syndrome in the index case followed by evaluation of family members and confirmation of genetic and ocular findings. We believe that this may be the first such report of families with RRD from India.
Anophthalmia and microphthalmia (A/M) are developmental ocular malformations in which the eye fails to form or is smaller than normal with both genetic and environmental etiology. Microphthalmia is often associated with additional ocular anomalies, most commonly coloboma or cataract [1,2]. A/M has a combined incidence between 1-3.2 cases per 10,000 live births in Caucasians [3,4]. The spectrum of genetic abnormalities (chromosomal and molecular) associated with these ocular developmental defects are being investigated in the current study. A detailed pedigree analysis and ophthalmic examination have
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.