Identification of a novel single nucleotide deletion in the NHS causing Nance-Horan syndrome
Abstract Background Nance–Horan syndrome (NHS) is a rare X-linked dominant disorder caused by pathogenic variants in the NHS gene on chromosome Xp22.2-Xp22.13. Clinical manifestations consist of congenital cataracts, along with dysmorphic facial features and dental anomalies and, in certain instance...
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BMC
2025-02-01
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| Series: | BMC Ophthalmology |
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| Online Access: | https://doi.org/10.1186/s12886-025-03933-z |
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| author | Teng Huang Ya-Nan Liu Dan-Tong Ding Qiao Wang Qiu-Ling Xie Xue-Chuan Miao Chuan Qin Xiu-Feng Huang Jin Li |
| author_facet | Teng Huang Ya-Nan Liu Dan-Tong Ding Qiao Wang Qiu-Ling Xie Xue-Chuan Miao Chuan Qin Xiu-Feng Huang Jin Li |
| author_sort | Teng Huang |
| collection | DOAJ |
| description | Abstract Background Nance–Horan syndrome (NHS) is a rare X-linked dominant disorder caused by pathogenic variants in the NHS gene on chromosome Xp22.2-Xp22.13. Clinical manifestations consist of congenital cataracts, along with dysmorphic facial features and dental anomalies and, in certain instances, intellectual disability. This study aimed to identify the genetic cause responsible for NHS in a Chinese family with four individuals primarily presenting with congenital cataracts. Methods Genomic DNA was collected from six family members, including four affected individuals (three females and one male) from a two-generation family. The family history and clinical data were documented. Whole-exome sequencing was performed on the proband, and candidate pathogenic variants were filtered through a series of screening steps and validated by Sanger sequencing. Co-segregation analysis was conducted to confirm the pathogenicity of the identified variant. Results Genetic analysis revealed a novel frameshift pathogenic variant in NHS gene (c.1735delA: p.R579Gfs*91) present in all four affected members. All affected members exhibited congenital cataracts, congenital ptosis, strabismus, high myopia as well as dental and facial anomalies, and more severe characteristic features observed in the male patient. These clinical manifestations were consistent with the phenotype of NHS. Conclusion This study identified a novel NHS pathogenic variant in a Chinese family, expanding the mutational spectrum of NHS. Contrary to previous reports of female carriers exhibiting mild symptoms, we demonstrated severe ocular phenotypes in three affected females. These findings will assist in providing genetic counseling for NHS patients. |
| format | Article |
| id | doaj-art-eb6f36c36a614c1d88162a0b5bcf39a9 |
| institution | OA Journals |
| issn | 1471-2415 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Ophthalmology |
| spelling | doaj-art-eb6f36c36a614c1d88162a0b5bcf39a92025-08-20T02:16:34ZengBMCBMC Ophthalmology1471-24152025-02-0125111310.1186/s12886-025-03933-zIdentification of a novel single nucleotide deletion in the NHS causing Nance-Horan syndromeTeng Huang0Ya-Nan Liu1Dan-Tong Ding2Qiao Wang3Qiu-Ling Xie4Xue-Chuan Miao5Chuan Qin6Xiu-Feng Huang7Jin Li8National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical UniversityNational Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical UniversityNational Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical UniversityNational Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical UniversityNational Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical UniversityNational Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical UniversityInstitute of PSI Genomics Co., LtdZhejiang Provincial Clinical Research Center for Pediatric DiseaseNational Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical UniversityAbstract Background Nance–Horan syndrome (NHS) is a rare X-linked dominant disorder caused by pathogenic variants in the NHS gene on chromosome Xp22.2-Xp22.13. Clinical manifestations consist of congenital cataracts, along with dysmorphic facial features and dental anomalies and, in certain instances, intellectual disability. This study aimed to identify the genetic cause responsible for NHS in a Chinese family with four individuals primarily presenting with congenital cataracts. Methods Genomic DNA was collected from six family members, including four affected individuals (three females and one male) from a two-generation family. The family history and clinical data were documented. Whole-exome sequencing was performed on the proband, and candidate pathogenic variants were filtered through a series of screening steps and validated by Sanger sequencing. Co-segregation analysis was conducted to confirm the pathogenicity of the identified variant. Results Genetic analysis revealed a novel frameshift pathogenic variant in NHS gene (c.1735delA: p.R579Gfs*91) present in all four affected members. All affected members exhibited congenital cataracts, congenital ptosis, strabismus, high myopia as well as dental and facial anomalies, and more severe characteristic features observed in the male patient. These clinical manifestations were consistent with the phenotype of NHS. Conclusion This study identified a novel NHS pathogenic variant in a Chinese family, expanding the mutational spectrum of NHS. Contrary to previous reports of female carriers exhibiting mild symptoms, we demonstrated severe ocular phenotypes in three affected females. These findings will assist in providing genetic counseling for NHS patients.https://doi.org/10.1186/s12886-025-03933-zNance-Horan syndromeNHSCongenital cataractsX-linked disease |
| spellingShingle | Teng Huang Ya-Nan Liu Dan-Tong Ding Qiao Wang Qiu-Ling Xie Xue-Chuan Miao Chuan Qin Xiu-Feng Huang Jin Li Identification of a novel single nucleotide deletion in the NHS causing Nance-Horan syndrome BMC Ophthalmology Nance-Horan syndrome NHS Congenital cataracts X-linked disease |
| title | Identification of a novel single nucleotide deletion in the NHS causing Nance-Horan syndrome |
| title_full | Identification of a novel single nucleotide deletion in the NHS causing Nance-Horan syndrome |
| title_fullStr | Identification of a novel single nucleotide deletion in the NHS causing Nance-Horan syndrome |
| title_full_unstemmed | Identification of a novel single nucleotide deletion in the NHS causing Nance-Horan syndrome |
| title_short | Identification of a novel single nucleotide deletion in the NHS causing Nance-Horan syndrome |
| title_sort | identification of a novel single nucleotide deletion in the nhs causing nance horan syndrome |
| topic | Nance-Horan syndrome NHS Congenital cataracts X-linked disease |
| url | https://doi.org/10.1186/s12886-025-03933-z |
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