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Abstract #94897 Published in IGR 22-2
Heterozygous variants with ocular phenotype: Missense in domain but truncation out of domain
Li X; Xiao X; Li S; Ouyang J; Sun W; Liu X; Zhang QMolecular Vision 2021; 27: 309-322
PURPOSE: Oculodentodigital dysplasia (ODDD) is a group disorder caused by variants, of which glaucoma leading to blindness is a frequent complication of the ocular phenotype. In this study, the correlation of the genotype with the ocular phenotype was analyzed systematically. METHODS: Array RESULTS: In total, 21 rare variants in were detected in 32 subjects from the study cohort. Four of the 21 variants were classified as PPVs, including two frameshift, one missense, and one in-frame deletion. The four PPVs were detected in four probands with microcornea or high hyperopia; two developed glaucoma. A systematic review of variants in literature suggested that most heterozygous missense PPVs are located inside the connexin domain. All truncations downstream of the connexin domain are associated with autosomal dominant disease, while most truncations within the domain are associated with autosomal recessive ODDD. Ocular signs were present in 80.0% (116/145) of patients with PPVs. Of the 116 patients, glaucoma was observed in 26.7% (31/116), among whom 77.4% (24/31) of cases occurred in patients ≥10 years old. CONCLUSIONS: Eye abnormalities are the most common signs associated with PPVs, and they carry a high risk of developing glaucoma. The identification of PPVs needs further attention and clarification.
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
Classification:
9.1.1 Congenital glaucoma, Buphthalmos (Part of: 9 Clinical forms of glaucomas > 9.1 Developmental glaucomas)
3.4.2 Gene studies (Part of: 3 Laboratory methods > 3.4 Molecular genetics)
3.5 Molecular biology incl. SiRNA (Part of: 3 Laboratory methods)
9.4.15 Glaucoma in relation to systemic disease (Part of: 9 Clinical forms of glaucomas > 9.4 Glaucomas associated with other ocular and systemic disorders)
