Novel compound heterozygous variants of the SEC23A gene in a Chinese family with cranio-lenticulo-sutural dysplasia based on data from a large cohort of congenital cataract patients
Abstract Background Cranio-lenticulo-sutural dysplasia (CLSD) is a rare dysmorphic syndrome characterized by skeletal dysmorphism, late-closing fontanels, and cataracts. CLSD is caused by mutations in the SEC23A gene (OMIM# 607812) and can be inherited in either an autosomal dominant or autosomal re...
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| Format: | Article |
| Language: | English |
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BMC
2023-10-01
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| Series: | BMC Medical Genomics |
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| Online Access: | https://doi.org/10.1186/s12920-023-01667-9 |
| _version_ | 1827707824435625984 |
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| author | Qiwei Wang Xiaoshan Lin Kunbei Lai Yinghui Liu Tingfeng Qin Haowen Tan Jing Li Zhuoling Lin Xulin Zhang Xiaoyan Li Haotian Lin Weirong Chen |
| author_facet | Qiwei Wang Xiaoshan Lin Kunbei Lai Yinghui Liu Tingfeng Qin Haowen Tan Jing Li Zhuoling Lin Xulin Zhang Xiaoyan Li Haotian Lin Weirong Chen |
| author_sort | Qiwei Wang |
| collection | DOAJ |
| description | Abstract Background Cranio-lenticulo-sutural dysplasia (CLSD) is a rare dysmorphic syndrome characterized by skeletal dysmorphism, late-closing fontanels, and cataracts. CLSD is caused by mutations in the SEC23A gene (OMIM# 607812) and can be inherited in either an autosomal dominant or autosomal recessive pattern. To date, only four mutations have been reported to cause CLSD. This study aims to identify the disease-causing variants in a large cohort of congenital cataract patients, to expand the genotypic and phenotypic spectrum of CLSD, and to confirm the association between SEC23A and autosomal recessive CLSD (ARCLSD). Methods We collected detailed medical records and performed comprehensive ocular examinations and whole-exome sequencing (WES) on 115 patients with congenital cataracts. After suspecting that a patient may have CLSD based on the sequencing results, we proceeded to conduct transmission electron microscopy (TEM) on the cultured skin fibroblasts. The clinical validity of the reported gene-disease relationships for the gene and the disease was evaluated using the ClinGen gene curation framework. Results Two novel compound heterozygous variants (c.710A > C p.Asp237Ala, c.1946T > C p.Leu649Pro) of the SEC23A gene, classified as variant of uncertain significance, were identified in the proband with skeletal, cardiac, ocular, and hearing defects. The observation of typical distended endoplasmic reticulum cisternae further supported the diagnosis of CLSD. Application of the ClinGen gene curation framework confirmed the association between SEC23A and ARCLSD. Conclusion This study expands the genotypic and phenotypic spectrum of CLSD, proposes TEM as a supplemental diagnostic method, and indicates that congenital cataracts are a typical sign of ARCLSD. |
| first_indexed | 2024-03-10T16:54:04Z |
| format | Article |
| id | doaj.art-8c0cf227f6ee4d70a15084df037e2619 |
| institution | Directory Open Access Journal |
| issn | 1755-8794 |
| language | English |
| last_indexed | 2024-03-10T16:54:04Z |
| publishDate | 2023-10-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medical Genomics |
| spelling | doaj.art-8c0cf227f6ee4d70a15084df037e26192023-11-20T11:13:22ZengBMCBMC Medical Genomics1755-87942023-10-011611710.1186/s12920-023-01667-9Novel compound heterozygous variants of the SEC23A gene in a Chinese family with cranio-lenticulo-sutural dysplasia based on data from a large cohort of congenital cataract patientsQiwei Wang0Xiaoshan Lin1Kunbei Lai2Yinghui Liu3Tingfeng Qin4Haowen Tan5Jing Li6Zhuoling Lin7Xulin Zhang8Xiaoyan Li9Haotian Lin10Weirong Chen11State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Centre, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Centre for Ocular Diseases, Sun Yat-sen UniversityState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Centre, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Centre for Ocular Diseases, Sun Yat-sen UniversityState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Centre, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Centre for Ocular Diseases, Sun Yat-sen UniversityDepartment of Dermatology, Dermatology Hospital, Southern Medical UniversityState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Centre, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Centre for Ocular Diseases, Sun Yat-sen UniversityAegicare BiotechState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Centre, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Centre for Ocular Diseases, Sun Yat-sen UniversityState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Centre, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Centre for Ocular Diseases, Sun Yat-sen UniversityState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Centre, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Centre for Ocular Diseases, Sun Yat-sen UniversityState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Centre, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Centre for Ocular Diseases, Sun Yat-sen UniversityState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Centre, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Centre for Ocular Diseases, Sun Yat-sen UniversityState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Centre, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Centre for Ocular Diseases, Sun Yat-sen UniversityAbstract Background Cranio-lenticulo-sutural dysplasia (CLSD) is a rare dysmorphic syndrome characterized by skeletal dysmorphism, late-closing fontanels, and cataracts. CLSD is caused by mutations in the SEC23A gene (OMIM# 607812) and can be inherited in either an autosomal dominant or autosomal recessive pattern. To date, only four mutations have been reported to cause CLSD. This study aims to identify the disease-causing variants in a large cohort of congenital cataract patients, to expand the genotypic and phenotypic spectrum of CLSD, and to confirm the association between SEC23A and autosomal recessive CLSD (ARCLSD). Methods We collected detailed medical records and performed comprehensive ocular examinations and whole-exome sequencing (WES) on 115 patients with congenital cataracts. After suspecting that a patient may have CLSD based on the sequencing results, we proceeded to conduct transmission electron microscopy (TEM) on the cultured skin fibroblasts. The clinical validity of the reported gene-disease relationships for the gene and the disease was evaluated using the ClinGen gene curation framework. Results Two novel compound heterozygous variants (c.710A > C p.Asp237Ala, c.1946T > C p.Leu649Pro) of the SEC23A gene, classified as variant of uncertain significance, were identified in the proband with skeletal, cardiac, ocular, and hearing defects. The observation of typical distended endoplasmic reticulum cisternae further supported the diagnosis of CLSD. Application of the ClinGen gene curation framework confirmed the association between SEC23A and ARCLSD. Conclusion This study expands the genotypic and phenotypic spectrum of CLSD, proposes TEM as a supplemental diagnostic method, and indicates that congenital cataracts are a typical sign of ARCLSD.https://doi.org/10.1186/s12920-023-01667-9SEC23ACongenital cataractCranio-lenticulo-sutural dysplasiaGene curationGenetic variants |
| spellingShingle | Qiwei Wang Xiaoshan Lin Kunbei Lai Yinghui Liu Tingfeng Qin Haowen Tan Jing Li Zhuoling Lin Xulin Zhang Xiaoyan Li Haotian Lin Weirong Chen Novel compound heterozygous variants of the SEC23A gene in a Chinese family with cranio-lenticulo-sutural dysplasia based on data from a large cohort of congenital cataract patients BMC Medical Genomics SEC23A Congenital cataract Cranio-lenticulo-sutural dysplasia Gene curation Genetic variants |
| title | Novel compound heterozygous variants of the SEC23A gene in a Chinese family with cranio-lenticulo-sutural dysplasia based on data from a large cohort of congenital cataract patients |
| title_full | Novel compound heterozygous variants of the SEC23A gene in a Chinese family with cranio-lenticulo-sutural dysplasia based on data from a large cohort of congenital cataract patients |
| title_fullStr | Novel compound heterozygous variants of the SEC23A gene in a Chinese family with cranio-lenticulo-sutural dysplasia based on data from a large cohort of congenital cataract patients |
| title_full_unstemmed | Novel compound heterozygous variants of the SEC23A gene in a Chinese family with cranio-lenticulo-sutural dysplasia based on data from a large cohort of congenital cataract patients |
| title_short | Novel compound heterozygous variants of the SEC23A gene in a Chinese family with cranio-lenticulo-sutural dysplasia based on data from a large cohort of congenital cataract patients |
| title_sort | novel compound heterozygous variants of the sec23a gene in a chinese family with cranio lenticulo sutural dysplasia based on data from a large cohort of congenital cataract patients |
| topic | SEC23A Congenital cataract Cranio-lenticulo-sutural dysplasia Gene curation Genetic variants |
| url | https://doi.org/10.1186/s12920-023-01667-9 |
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