Mutation Spectrum and De Novo Mutation Analysis in Stickler Syndrome Patients with High Myopia or Retinal Detachment.

Li Huang,Chonglin Chen,Songshan Li,Zhirong Wang,Ting Zhang,Limei Sun,Xiaoyan Ding,Xiaoling Luo

doi:10.3390/genes11080882

Abstract

Stickler syndrome is a connective tissue disorder that affects multiple systems, including the visual system. Seven genes were reported to cause Stickler syndrome in patients with different phenotypes. In this study, we aimed to evaluate the mutation features of the phenotypes of high myopia and retinal detachment. Forty-two probands diagnosed with Stickler syndrome were included. Comprehensive ocular examinations were performed. A targeted gene panel test or whole exome sequencing was used to detect the mutations, and Sanger sequencing was conducted for verification and segregation analysis. Among the 42 probands, 32 (76%) presented with high myopia and 29 (69%), with retinal detachment. Pathogenic mutations were detected in 35 (83%) probands: 27 (64%) probands had COL2A1 mutations, and eight (19%) probands had COL11A1 mutations. Truncational mutations in COL2A1 were present in 21 (78%) probands. Missense mutations in COL2A1 were present in six probands, five of which presented with retinal detachment. De novo COL2A1 mutations were detected in 10 (37%) probands, with a mean paternal childbearing age of 29.64 ± 4.97 years old. The mutation features of probands with high myopia or retinal detachment showed that the probands had a high prevalence of COL2A1 mutations, truncational mutations, and de novo mutations.

Highlights

Stickler syndrome is a connective tissue disorder that was first reported by Stickler et al in 1965 [1].The characteristics of Stickler syndrome include ocular findings of myopia, cataracts, and retinal detachment; hearing loss that is both conductive and sensorineural; midfacial underdevelopment and cleft palate; and mild spondyloepiphyseal dysplasia and/or precocious arthritis [2]
COL2A1, COL11A1, and COL11A2 mutations are inherited as autosomal dominant traits, whereas COL9A1, COL9A2, COL9A3, and LOXL3 mutations are inherited as recessive traits [2]
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Summary

Introduction

The characteristics of Stickler syndrome include ocular findings of myopia, cataracts, and retinal detachment; hearing loss that is both conductive and sensorineural; midfacial underdevelopment and cleft palate (either alone or as part of the Robin sequence); and mild spondyloepiphyseal dysplasia and/or precocious arthritis [2]. Mutations in the following genes are considered causative of Stickler syndrome: COL2A1 120270) [9], and LOXL3 In patients with COL2A1 mutations, myopia is the most common sign, which is present in 90% of patients, followed by vitreous changes, detected in 40% of patients, and cataracts, in 30% of patients.

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