The mutation spectrum in familial versus sporadic congenital cataract based on next-generation sequencing
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RESEARCH ARTICLE
Open Access
The mutation spectrum in familial versus sporadic congenital cataract based on nextgeneration sequencing Fan Fan1,2,3, Yi Luo1,2,3* , Jihong Wu1,2,3, Chao Gao1,2,3, Xin Liu1,2,3, Hengjun Mei1,2,3 and Xiyue Zhou1,2,3
Abstract Background: Congenital cataract (CC) is a significant cause of lifelong visual loss, and its genetic diagnosis is challenging due to marked genetic heterogeneity. The purpose of this article is to report the genetic findings in sporadic and familial CC patients. Methods: Patients (n = 53) who were clinically diagnosed with CC and their parents were recruited. Blood samples were collected in our hospital. Mutations were detected by panel-based next-generation DNA sequencing (NGS) targeting 792 genes frequently involved in common inherited eye diseases. Results: We identified variants in 10/37 cases (27.02%) of sporadic CC and 14/16 cases (87.5%) of familial CC, which indicated a significant difference (P = 0.000). Of the 13 variants identified in sporadic cases, nine were previously reported mutations, and three were novel mutations, including one de novo mutation (CRYBB2 c.487C > T). The most frequent variants in our cohort were in crystallins and cytoskeletal genes (5/27, 18.52%), followed by proteins associated with X-linked syndromic conditions (14.81%) and transcriptional factors (11.11%). Additional information on the possibility of complications with inherited ocular or systemic diseases other than CC was provided in 17/27 (62.96%) variants. Conclusions: These results contribute to expanding the mutation spectrum and frequency of genes responsible for CC. Targeted NGS in CC provided significant diagnostic information and enabled more accurate genetic counselling. This study reports the different distributions of mutation genes in familial and sporadic CC cases. Keywords: Congenital cataract, Gene mutation, Sporadic, Familial, NGS, Mutation spectrum, Next-generation sequencing
Background Congenital cataracts (CCs) are now the most common avoidable cause of childhood blindness worldwide, accounting for 10–35% of such cases, with an estimated incidence of 0.63–9.14/10,000 births [1–4]. Management is often difficult due to the risk of amblyopia in the * Correspondence: [email protected] 1 Department of Ophthalmology, Eye and Ear, Nose, and Throat Hospital, Fudan University, Shanghai, China 2 Eye Institute, Eye and Ear, Nose, and Throat Hospital, Fudan University, Shanghai, China Full list of author information is available at the end of the article
developing visual system and complications of glaucoma, posterior synechia or visual axis opacification, which require additional surgery [5]. CCs occur due to the disruption of the lens microarchitecture or the protein function in the lens [6]. Except for a very few infectious cases, only one-third of CC cases have a positive family history [7], with the other two-thirds having an unknown aetiology [8]. Therefore, a significant proportion are sporadic cases in which it is not known whether there is an underlying
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