CUX1 variant and 9p deletion: expanding the spectrum and resolving variable GDD/ID in a family
Abstract Background Intellectual disability (ID) significantly impacts individual development and imposes a societal burden. Although mild ID accounts for approximately 85% of total cases, research into its genetic etiology remains relatively limited. We investigated a two-generation pedigree exhibi...
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BMC
2025-08-01
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| Series: | BMC Medical Genomics |
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| Online Access: | https://doi.org/10.1186/s12920-025-02203-7 |
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| author | Haiting Liu Xiaoyong Liu Ximin Chen Yangmei Pu Wen Liu Zemin Luo Ai Chen Hui Zhu Fu Xiong Lan Zeng Jin Wang Xiaocheng Nie Shuyao Zhu |
| author_facet | Haiting Liu Xiaoyong Liu Ximin Chen Yangmei Pu Wen Liu Zemin Luo Ai Chen Hui Zhu Fu Xiong Lan Zeng Jin Wang Xiaocheng Nie Shuyao Zhu |
| author_sort | Haiting Liu |
| collection | DOAJ |
| description | Abstract Background Intellectual disability (ID) significantly impacts individual development and imposes a societal burden. Although mild ID accounts for approximately 85% of total cases, research into its genetic etiology remains relatively limited. We investigated a two-generation pedigree exhibiting varying degrees of global developmental delay (GDD) and ID. We collected clinical data from the proband and her parents, identified the genetic etiology through testing, investigated pathogenic mechanisms, and provided family genetic counseling. Methods Peripheral blood samples were collected from pedigree members for chromosomal karyotyping and genomic DNA extraction. Trio exome sequencing (Trio-ES) was performed on the DNA samples. Candidate variants identified were validated using Sanger sequencing, and their pathogenicity was assessed in accordance with the standards and guidelines of the American College of Medical Genetics and Genomics (ACMG). Results The proband, a 2-year-old female, presented with GDD. Her father exhibited borderline intellectual disability, while her mother had mild intellectual disability. ES analysis revealed: Exome sequencing identified a unknown inheritance heterozygous variant (NM_001202543.2[CUX1]: c.2637G > A [p.Trp879*]) in both the proband and her father, classified as likely pathogenic. The mother carried an 8.60 Mb deletion (seq[hg19]del(9)(p24.3p24.1), which was classified as a pathogenic copy number variant (CNV). Conclusion Our findings expand the spectrum of genetic variations associated with CUX1-related disorders. The conclusive molecular diagnosis established through genetic testing not only facilitated accurate genetic counseling but also reduced the time and economic burdens associated with the diagnostic odyssey. |
| format | Article |
| id | doaj-art-26239ee8892d4ee4a322e278ae77877e |
| institution | Kabale University |
| issn | 1755-8794 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medical Genomics |
| spelling | doaj-art-26239ee8892d4ee4a322e278ae77877e2025-08-24T11:56:16ZengBMCBMC Medical Genomics1755-87942025-08-011811910.1186/s12920-025-02203-7CUX1 variant and 9p deletion: expanding the spectrum and resolving variable GDD/ID in a familyHaiting Liu0Xiaoyong Liu1Ximin Chen2Yangmei Pu3Wen Liu4Zemin Luo5Ai Chen6Hui Zhu7Fu Xiong8Lan Zeng9Jin Wang10Xiaocheng Nie11Shuyao Zhu12Department of Neonatology, West China Second University Hospital, Sichuan University/West China women’s and children’s hospitalDepartment of Medical Genetics and Prenatal Diagnosis, Sichuan Provincial Woman’s and Children’s HospitalDepartment of Pediatrics, Sichuan Provincial Woman’s and Children’s HospitalDepartment of Radiology, Sichuan Provincial Woman’s and Children’s HospitalDepartment of Medical Genetics and Prenatal Diagnosis, Sichuan Provincial Woman’s and Children’s HospitalDepartment of Medical Genetics and Prenatal Diagnosis, Sichuan Provincial Woman’s and Children’s HospitalDepartment of Pediatrics, The Second People’s Hospital of Chengdu CityDepartment of Medical Genetics and Prenatal Diagnosis, Sichuan Provincial Woman’s and Children’s HospitalDepartment of Medical Genetics and Prenatal Diagnosis, Sichuan Provincial Woman’s and Children’s HospitalDepartment of Pediatrics, Sichuan Provincial Woman’s and Children’s HospitalDepartment of Pediatrics, Sichuan Provincial Woman’s and Children’s HospitalDepartment of Gynecology and Obstetrics, Sichuan Provincial Woman’s and Children’s HospitalDepartment of Medical Genetics and Prenatal Diagnosis, Sichuan Provincial Woman’s and Children’s HospitalAbstract Background Intellectual disability (ID) significantly impacts individual development and imposes a societal burden. Although mild ID accounts for approximately 85% of total cases, research into its genetic etiology remains relatively limited. We investigated a two-generation pedigree exhibiting varying degrees of global developmental delay (GDD) and ID. We collected clinical data from the proband and her parents, identified the genetic etiology through testing, investigated pathogenic mechanisms, and provided family genetic counseling. Methods Peripheral blood samples were collected from pedigree members for chromosomal karyotyping and genomic DNA extraction. Trio exome sequencing (Trio-ES) was performed on the DNA samples. Candidate variants identified were validated using Sanger sequencing, and their pathogenicity was assessed in accordance with the standards and guidelines of the American College of Medical Genetics and Genomics (ACMG). Results The proband, a 2-year-old female, presented with GDD. Her father exhibited borderline intellectual disability, while her mother had mild intellectual disability. ES analysis revealed: Exome sequencing identified a unknown inheritance heterozygous variant (NM_001202543.2[CUX1]: c.2637G > A [p.Trp879*]) in both the proband and her father, classified as likely pathogenic. The mother carried an 8.60 Mb deletion (seq[hg19]del(9)(p24.3p24.1), which was classified as a pathogenic copy number variant (CNV). Conclusion Our findings expand the spectrum of genetic variations associated with CUX1-related disorders. The conclusive molecular diagnosis established through genetic testing not only facilitated accurate genetic counseling but also reduced the time and economic burdens associated with the diagnostic odyssey.https://doi.org/10.1186/s12920-025-02203-7CUX19p deletionIntellectual disabilityExome sequencing |
| spellingShingle | Haiting Liu Xiaoyong Liu Ximin Chen Yangmei Pu Wen Liu Zemin Luo Ai Chen Hui Zhu Fu Xiong Lan Zeng Jin Wang Xiaocheng Nie Shuyao Zhu CUX1 variant and 9p deletion: expanding the spectrum and resolving variable GDD/ID in a family BMC Medical Genomics CUX1 9p deletion Intellectual disability Exome sequencing |
| title | CUX1 variant and 9p deletion: expanding the spectrum and resolving variable GDD/ID in a family |
| title_full | CUX1 variant and 9p deletion: expanding the spectrum and resolving variable GDD/ID in a family |
| title_fullStr | CUX1 variant and 9p deletion: expanding the spectrum and resolving variable GDD/ID in a family |
| title_full_unstemmed | CUX1 variant and 9p deletion: expanding the spectrum and resolving variable GDD/ID in a family |
| title_short | CUX1 variant and 9p deletion: expanding the spectrum and resolving variable GDD/ID in a family |
| title_sort | cux1 variant and 9p deletion expanding the spectrum and resolving variable gdd id in a family |
| topic | CUX1 9p deletion Intellectual disability Exome sequencing |
| url | https://doi.org/10.1186/s12920-025-02203-7 |
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