Case Report: The nonsense variation of the cardiac transcription factor NKX2-5 has been identified in a Chinese family with nonsyndromic congenital heart disease
BackgroundNK2 HOMEOBOX 5(OMIM: 600584, NKX2-5), a pivotal cardiac regulatory transcription factor, represents the initial identified genetic etiology underlying congenital heart diseases (CHDs). As a member of the NK homeobox gene family, NKX2-5 functions as an essential DNA-binding transcriptional...
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Frontiers Media S.A.
2025-07-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2025.1498144/full |
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| author | Haixia Zhang Haixia Zhang Jing Chen Jing Chen He Wang He Wang Qinqin Xiang Qinqin Xiang Shanling Liu Shanling Liu |
| author_facet | Haixia Zhang Haixia Zhang Jing Chen Jing Chen He Wang He Wang Qinqin Xiang Qinqin Xiang Shanling Liu Shanling Liu |
| author_sort | Haixia Zhang |
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| description | BackgroundNK2 HOMEOBOX 5(OMIM: 600584, NKX2-5), a pivotal cardiac regulatory transcription factor, represents the initial identified genetic etiology underlying congenital heart diseases (CHDs). As a member of the NK homeobox gene family, NKX2-5 functions as an essential DNA-binding transcriptional activator. It demonstrates robust expression levels in both primary and secondary heart fields’ cardiac progenitor cells, playing an indispensable role in cardiovascular development. Here we reported a NKX2-5 nonsense variant in a Chinese family with nonsyndromic congenital heart disease.Case presentationTrio-whole-exome sequencing (Trio-WES) was performed on the proband and parents, followed by Sanger sequencing for verification and linkage analysis using available DNA samples from this family and additional family members. A nonsense variant (NM_004387.4: c.342C>A, p.(Cys114*)) was identified within the NKX2-5 gene through Trio-WES analysis and classified as likely pathogenic according to the criteria of the ACMG. Sanger sequencing revealed the presence of this nonsense variant in all affected family members (II1, II3, III1, and III5) within the NKX2-5 gene, while unaffected family members (II2, II7, and II8) did not exhibit this variant.ConclusionThe present study identified a heterozygous nonsense variant of the NKX2-5 gene in a family with nonsyndromic congenital heart disease, suggesting that this variant may be the underlying cause of the disease within this particular family. Our findings suggests that it can cause diverse phenotypes and varying severity of cardiac abnormalities even within the family. Additionally, an early and definitive genetic diagnosis can provide precise information for subsequent treatment and fertility counseling. |
| format | Article |
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| institution | Kabale University |
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| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Genetics |
| spelling | doaj-art-e2b20c08bf1c435fb8619a51ef46faed2025-08-20T03:28:14ZengFrontiers Media S.A.Frontiers in Genetics1664-80212025-07-011610.3389/fgene.2025.14981441498144Case Report: The nonsense variation of the cardiac transcription factor NKX2-5 has been identified in a Chinese family with nonsyndromic congenital heart diseaseHaixia Zhang0Haixia Zhang1Jing Chen2Jing Chen3He Wang4He Wang5Qinqin Xiang6Qinqin Xiang7Shanling Liu8Shanling Liu9Department of Medical Genetics/Prenatal Diagnostic Center, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, ChinaKey Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, Sichuan, ChinaDepartment of Medical Genetics/Prenatal Diagnostic Center, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, ChinaKey Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, Sichuan, ChinaDepartment of Medical Genetics/Prenatal Diagnostic Center, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, ChinaKey Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, Sichuan, ChinaDepartment of Medical Genetics/Prenatal Diagnostic Center, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, ChinaKey Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, Sichuan, ChinaDepartment of Medical Genetics/Prenatal Diagnostic Center, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, ChinaKey Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, Sichuan, ChinaBackgroundNK2 HOMEOBOX 5(OMIM: 600584, NKX2-5), a pivotal cardiac regulatory transcription factor, represents the initial identified genetic etiology underlying congenital heart diseases (CHDs). As a member of the NK homeobox gene family, NKX2-5 functions as an essential DNA-binding transcriptional activator. It demonstrates robust expression levels in both primary and secondary heart fields’ cardiac progenitor cells, playing an indispensable role in cardiovascular development. Here we reported a NKX2-5 nonsense variant in a Chinese family with nonsyndromic congenital heart disease.Case presentationTrio-whole-exome sequencing (Trio-WES) was performed on the proband and parents, followed by Sanger sequencing for verification and linkage analysis using available DNA samples from this family and additional family members. A nonsense variant (NM_004387.4: c.342C>A, p.(Cys114*)) was identified within the NKX2-5 gene through Trio-WES analysis and classified as likely pathogenic according to the criteria of the ACMG. Sanger sequencing revealed the presence of this nonsense variant in all affected family members (II1, II3, III1, and III5) within the NKX2-5 gene, while unaffected family members (II2, II7, and II8) did not exhibit this variant.ConclusionThe present study identified a heterozygous nonsense variant of the NKX2-5 gene in a family with nonsyndromic congenital heart disease, suggesting that this variant may be the underlying cause of the disease within this particular family. Our findings suggests that it can cause diverse phenotypes and varying severity of cardiac abnormalities even within the family. Additionally, an early and definitive genetic diagnosis can provide precise information for subsequent treatment and fertility counseling.https://www.frontiersin.org/articles/10.3389/fgene.2025.1498144/fullnkx2-5nonsense varianttrio-whole-exome sequencingnonsyndromic congenital heart diseasecase report |
| spellingShingle | Haixia Zhang Haixia Zhang Jing Chen Jing Chen He Wang He Wang Qinqin Xiang Qinqin Xiang Shanling Liu Shanling Liu Case Report: The nonsense variation of the cardiac transcription factor NKX2-5 has been identified in a Chinese family with nonsyndromic congenital heart disease Frontiers in Genetics nkx2-5 nonsense variant trio-whole-exome sequencing nonsyndromic congenital heart disease case report |
| title | Case Report: The nonsense variation of the cardiac transcription factor NKX2-5 has been identified in a Chinese family with nonsyndromic congenital heart disease |
| title_full | Case Report: The nonsense variation of the cardiac transcription factor NKX2-5 has been identified in a Chinese family with nonsyndromic congenital heart disease |
| title_fullStr | Case Report: The nonsense variation of the cardiac transcription factor NKX2-5 has been identified in a Chinese family with nonsyndromic congenital heart disease |
| title_full_unstemmed | Case Report: The nonsense variation of the cardiac transcription factor NKX2-5 has been identified in a Chinese family with nonsyndromic congenital heart disease |
| title_short | Case Report: The nonsense variation of the cardiac transcription factor NKX2-5 has been identified in a Chinese family with nonsyndromic congenital heart disease |
| title_sort | case report the nonsense variation of the cardiac transcription factor nkx2 5 has been identified in a chinese family with nonsyndromic congenital heart disease |
| topic | nkx2-5 nonsense variant trio-whole-exome sequencing nonsyndromic congenital heart disease case report |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2025.1498144/full |
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