Whole-exome sequencing uncovers the genetic basis of hereditary concomitant exotropia in ten Chinese pedigrees
Abstract Purpose To explore possible pathogenic genes for concomitant exotropia using whole-exome sequencing. Methods In this study, 47 individuals from 10 concomitant exotropia (including intermittent exotropia and constant exotropia) pedigrees were enrolled. Whole-exome sequencing was used to scre...
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BMC
2025-01-01
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| Series: | BMC Medical Genomics |
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| Online Access: | https://doi.org/10.1186/s12920-024-02078-0 |
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| author | Wenhua Duan Taicheng Zhou Xiaoru Huang Dongqiong He Min Hu |
| author_facet | Wenhua Duan Taicheng Zhou Xiaoru Huang Dongqiong He Min Hu |
| author_sort | Wenhua Duan |
| collection | DOAJ |
| description | Abstract Purpose To explore possible pathogenic genes for concomitant exotropia using whole-exome sequencing. Methods In this study, 47 individuals from 10 concomitant exotropia (including intermittent exotropia and constant exotropia) pedigrees were enrolled. Whole-exome sequencing was used to screen mutational profiles in 25 affected individuals and 10 unaffected individuals. Sanger sequencing and in silico analysis were performed for all participants. Two target genes were used to capture the sequences of 220 sporadic samples. Results All 10 concomitant exotropia pedigrees presented autosomal dominant inheritance with childhood onset (3.35 ± 1.51 years old). Eleven different missense variants were identified among seven potential pathogenic genes (COL4A2, SYNE1, LOXHD1, AUTS2, GTDC2, HERC2 and CDH3) that cosegregated with pedigree members. All variants were predicted to be deleterious and had low frequencies in the general population. Distinct variants of COL4A2 were present in three pedigrees, and distinct variants of SYNE1 were present in two pedigrees. Fifteen variants in AUTS2 and four variants in GTDC2 were identified in 220 patients with sporadic concomitant exotropia using a target-capture sequencing approach. Conclusion This is the first study to explore the genetic mechanism of concomitant exotropia and identify seven associated genes (COL4A2, SYNE1, LOXHD1, AUTS2, GTDC2, HERC2 and CDH3) that may be candidate genes causing concomitant exotropia. More samples and in-depth studies are needed to verify these findings. |
| format | Article |
| id | doaj-art-288fcd6932eb48529ae147c0eeadf260 |
| institution | Kabale University |
| issn | 1755-8794 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
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| series | BMC Medical Genomics |
| spelling | doaj-art-288fcd6932eb48529ae147c0eeadf2602025-01-12T12:43:37ZengBMCBMC Medical Genomics1755-87942025-01-0118111110.1186/s12920-024-02078-0Whole-exome sequencing uncovers the genetic basis of hereditary concomitant exotropia in ten Chinese pedigreesWenhua Duan0Taicheng Zhou1Xiaoru Huang2Dongqiong He3Min Hu4The First People’s Hospital of Yunnan Province (The Affiliated Hospital of Kunming University of Science and Technology)The Affiliated Hospital of Yunnan University (The Second People’s Hospital of Yunnan Province)Yunnan UniversityThe First People’s Hospital of Yunnan Province (The Affiliated Hospital of Kunming University of Science and Technology)The Affiliated Hospital of Yunnan University (The Second People’s Hospital of Yunnan Province)Abstract Purpose To explore possible pathogenic genes for concomitant exotropia using whole-exome sequencing. Methods In this study, 47 individuals from 10 concomitant exotropia (including intermittent exotropia and constant exotropia) pedigrees were enrolled. Whole-exome sequencing was used to screen mutational profiles in 25 affected individuals and 10 unaffected individuals. Sanger sequencing and in silico analysis were performed for all participants. Two target genes were used to capture the sequences of 220 sporadic samples. Results All 10 concomitant exotropia pedigrees presented autosomal dominant inheritance with childhood onset (3.35 ± 1.51 years old). Eleven different missense variants were identified among seven potential pathogenic genes (COL4A2, SYNE1, LOXHD1, AUTS2, GTDC2, HERC2 and CDH3) that cosegregated with pedigree members. All variants were predicted to be deleterious and had low frequencies in the general population. Distinct variants of COL4A2 were present in three pedigrees, and distinct variants of SYNE1 were present in two pedigrees. Fifteen variants in AUTS2 and four variants in GTDC2 were identified in 220 patients with sporadic concomitant exotropia using a target-capture sequencing approach. Conclusion This is the first study to explore the genetic mechanism of concomitant exotropia and identify seven associated genes (COL4A2, SYNE1, LOXHD1, AUTS2, GTDC2, HERC2 and CDH3) that may be candidate genes causing concomitant exotropia. More samples and in-depth studies are needed to verify these findings.https://doi.org/10.1186/s12920-024-02078-0GeneticsConcomitant exotropiaStrabismus |
| spellingShingle | Wenhua Duan Taicheng Zhou Xiaoru Huang Dongqiong He Min Hu Whole-exome sequencing uncovers the genetic basis of hereditary concomitant exotropia in ten Chinese pedigrees BMC Medical Genomics Genetics Concomitant exotropia Strabismus |
| title | Whole-exome sequencing uncovers the genetic basis of hereditary concomitant exotropia in ten Chinese pedigrees |
| title_full | Whole-exome sequencing uncovers the genetic basis of hereditary concomitant exotropia in ten Chinese pedigrees |
| title_fullStr | Whole-exome sequencing uncovers the genetic basis of hereditary concomitant exotropia in ten Chinese pedigrees |
| title_full_unstemmed | Whole-exome sequencing uncovers the genetic basis of hereditary concomitant exotropia in ten Chinese pedigrees |
| title_short | Whole-exome sequencing uncovers the genetic basis of hereditary concomitant exotropia in ten Chinese pedigrees |
| title_sort | whole exome sequencing uncovers the genetic basis of hereditary concomitant exotropia in ten chinese pedigrees |
| topic | Genetics Concomitant exotropia Strabismus |
| url | https://doi.org/10.1186/s12920-024-02078-0 |
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