Novel mutations in CRYBB1/CRYBB2 identified by targeted exome sequencing in Chinese families with congenital cataract
AIM: To summarize the phenotypes and identify the underlying genetic cause of the CRYBB1 and CRYBB2 gene responsible for congenital cataract in two Chinese families. METHODS: Detailed family histories and clinical data were collected from patients during an ophthalmologic examination. Of 523 inheri...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Press of International Journal of Ophthalmology (IJO PRESS)
2018-10-01
|
| Series: | International Journal of Ophthalmology |
| Subjects: | |
| Online Access: | http://www.ijo.cn/en_publish/2018/10/20181001.pdf |
| _version_ | 1818141524801617920 |
|---|---|
| author | Peng Chen Hao Chen Xiao-Jing Pan Su-Zhen Tang Yu-Jun Xia Hui Zhang |
| author_facet | Peng Chen Hao Chen Xiao-Jing Pan Su-Zhen Tang Yu-Jun Xia Hui Zhang |
| author_sort | Peng Chen |
| collection | DOAJ |
| description | AIM: To summarize the phenotypes and identify the underlying genetic cause of the CRYBB1 and CRYBB2 gene responsible for congenital cataract in two Chinese families.
METHODS: Detailed family histories and clinical data were collected from patients during an ophthalmologic examination. Of 523 inheritable genetic vision system-related genes were captured and sequenced by targeted next-generation sequencing, and the results were confirmed by Sanger sequencing. The possible functional impacts of an amino acid substitution were performed with PolyPhen-2 and SIFT predictions.
RESULTS: The patients in the two families were affected with congenital cataract. Sixty-five (FAMILY-1) and sixty-two (FAMILY-2) single-nucleotide polymorphisms and indels were selected by recommended filtering criteria. Segregation was then analyzed by applying Sanger sequencing with the family members. A heterozygous CRYBB1 mutation in exon 4 (c.347T>C, p.L116P) was identified in sixteen patients in FAMILY-1. A heterozygous CRYBB2 mutation in exon 5 (c.355G>A, p.G119R) was identified in three patients in FAMILY-2. Each mutation co-segregated with the affected individuals and did not exist in unaffected family members and 200 unrelated normal controls. The mutation was predicted to be highly conservative and to be deleterious by both PolyPhen-2 and SIFT.
CONCLUSION: The CRYBB1 mutation (c.347T>C) and CRYBB2 mutation (c.355G>A) are novel in patients with congenital cataract. We summarize the variable phenotypes among the patients, which expanded the phenotypic spectrum of congenital cataract in a different ethnic background. |
| first_indexed | 2024-12-11T11:01:15Z |
| format | Article |
| id | doaj.art-e4636f1b511c4f69a9a8ee082a3a9ce1 |
| institution | Directory Open Access Journal |
| issn | 2222-3959 2227-4898 |
| language | English |
| last_indexed | 2024-12-11T11:01:15Z |
| publishDate | 2018-10-01 |
| publisher | Press of International Journal of Ophthalmology (IJO PRESS) |
| record_format | Article |
| series | International Journal of Ophthalmology |
| spelling | doaj.art-e4636f1b511c4f69a9a8ee082a3a9ce12022-12-22T01:09:53ZengPress of International Journal of Ophthalmology (IJO PRESS)International Journal of Ophthalmology2222-39592227-48982018-10-0111101577158210.18240/ijo.2018.10.01Novel mutations in CRYBB1/CRYBB2 identified by targeted exome sequencing in Chinese families with congenital cataractPeng Chen0Hao Chen1Xiao-Jing Pan2Su-Zhen Tang3Yu-Jun Xia4Hui Zhang5Qingdao University, Qingdao 266071, Shandong Province, ChinaQingdao University, Qingdao 266071, Shandong Province, ChinaShandong Eye Institute, Qingdao 266071, Shandong Province, ChinaQingdao University, Qingdao 266071, Shandong Province, ChinaQingdao University, Qingdao 266071, Shandong Province, ChinaJinan Second People’s Hospital, Jinan 250022, Shandong Province, ChinaAIM: To summarize the phenotypes and identify the underlying genetic cause of the CRYBB1 and CRYBB2 gene responsible for congenital cataract in two Chinese families. METHODS: Detailed family histories and clinical data were collected from patients during an ophthalmologic examination. Of 523 inheritable genetic vision system-related genes were captured and sequenced by targeted next-generation sequencing, and the results were confirmed by Sanger sequencing. The possible functional impacts of an amino acid substitution were performed with PolyPhen-2 and SIFT predictions. RESULTS: The patients in the two families were affected with congenital cataract. Sixty-five (FAMILY-1) and sixty-two (FAMILY-2) single-nucleotide polymorphisms and indels were selected by recommended filtering criteria. Segregation was then analyzed by applying Sanger sequencing with the family members. A heterozygous CRYBB1 mutation in exon 4 (c.347T>C, p.L116P) was identified in sixteen patients in FAMILY-1. A heterozygous CRYBB2 mutation in exon 5 (c.355G>A, p.G119R) was identified in three patients in FAMILY-2. Each mutation co-segregated with the affected individuals and did not exist in unaffected family members and 200 unrelated normal controls. The mutation was predicted to be highly conservative and to be deleterious by both PolyPhen-2 and SIFT. CONCLUSION: The CRYBB1 mutation (c.347T>C) and CRYBB2 mutation (c.355G>A) are novel in patients with congenital cataract. We summarize the variable phenotypes among the patients, which expanded the phenotypic spectrum of congenital cataract in a different ethnic background.http://www.ijo.cn/en_publish/2018/10/20181001.pdfCRYBB1CRYBB2next-generation sequencingcongenital cataract |
| spellingShingle | Peng Chen Hao Chen Xiao-Jing Pan Su-Zhen Tang Yu-Jun Xia Hui Zhang Novel mutations in CRYBB1/CRYBB2 identified by targeted exome sequencing in Chinese families with congenital cataract International Journal of Ophthalmology CRYBB1 CRYBB2 next-generation sequencing congenital cataract |
| title | Novel mutations in CRYBB1/CRYBB2 identified by targeted exome sequencing in Chinese families with congenital cataract |
| title_full | Novel mutations in CRYBB1/CRYBB2 identified by targeted exome sequencing in Chinese families with congenital cataract |
| title_fullStr | Novel mutations in CRYBB1/CRYBB2 identified by targeted exome sequencing in Chinese families with congenital cataract |
| title_full_unstemmed | Novel mutations in CRYBB1/CRYBB2 identified by targeted exome sequencing in Chinese families with congenital cataract |
| title_short | Novel mutations in CRYBB1/CRYBB2 identified by targeted exome sequencing in Chinese families with congenital cataract |
| title_sort | novel mutations in crybb1 crybb2 identified by targeted exome sequencing in chinese families with congenital cataract |
| topic | CRYBB1 CRYBB2 next-generation sequencing congenital cataract |
| url | http://www.ijo.cn/en_publish/2018/10/20181001.pdf |
| work_keys_str_mv | AT pengchen novelmutationsincrybb1crybb2identifiedbytargetedexomesequencinginchinesefamilieswithcongenitalcataract AT haochen novelmutationsincrybb1crybb2identifiedbytargetedexomesequencinginchinesefamilieswithcongenitalcataract AT xiaojingpan novelmutationsincrybb1crybb2identifiedbytargetedexomesequencinginchinesefamilieswithcongenitalcataract AT suzhentang novelmutationsincrybb1crybb2identifiedbytargetedexomesequencinginchinesefamilieswithcongenitalcataract AT yujunxia novelmutationsincrybb1crybb2identifiedbytargetedexomesequencinginchinesefamilieswithcongenitalcataract AT huizhang novelmutationsincrybb1crybb2identifiedbytargetedexomesequencinginchinesefamilieswithcongenitalcataract |