Clinical Features and Genetic Characteristics of XLID Patients With KDM5C Gene Mutations: Insights on Phenotype–Genotype Correlations From 175 Previous Cases and Identification of a Novel Variant
ABSTRACT Background X‐linked intellectual disability (XLID) is a genetically heterogeneous disorder that results in cognitive impairment and developmental delays. Mutations in the KDM5C gene have been identified as a causative factor in XLID. This study aimed to identify novel variants associated wi...
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| Format: | Article |
| Language: | English |
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Wiley
2025-01-01
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| Series: | Molecular Genetics & Genomic Medicine |
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| Online Access: | https://doi.org/10.1002/mgg3.70057 |
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| author | Mohammad‐Reza Ghasemi Zahra Esmaeilizadeh Sahand Tehrani Fateh Hossein Sadeghi Saman Bagheri Farzad Hashemi‐Gorji Morteza Sheikhi Nooshabadi Rasoul Madannezhad Toktam Sadat Tavabe Ghavami Reza Mirfakhraie Mohammad Miryounesi |
| author_facet | Mohammad‐Reza Ghasemi Zahra Esmaeilizadeh Sahand Tehrani Fateh Hossein Sadeghi Saman Bagheri Farzad Hashemi‐Gorji Morteza Sheikhi Nooshabadi Rasoul Madannezhad Toktam Sadat Tavabe Ghavami Reza Mirfakhraie Mohammad Miryounesi |
| author_sort | Mohammad‐Reza Ghasemi |
| collection | DOAJ |
| description | ABSTRACT Background X‐linked intellectual disability (XLID) is a genetically heterogeneous disorder that results in cognitive impairment and developmental delays. Mutations in the KDM5C gene have been identified as a causative factor in XLID. This study aimed to identify novel variants associated with XLID and to investigate the clinical and genetic characteristics of XLID patients with mutations in the KDM5C gene. This study also conducted a narrative review of the literature to identify key clinical and genetic characteristics of XLID caused by mutations in the KDM5C gene. Study Design Whole‐exome sequencing was performed on the proband's DNA, and Sanger sequencing was used to confirm and analyze the identified variant in a 20‐month‐old male patient with motor and speech delays. Moreover, a comprehensive literature review was conducted to gather previously reported cases, providing insights into the molecular findings and clinical characteristics of this disorder. Results The study identified a novel variant, c.2704C>T:p.Gln902X, located in exon 19 of the KDM5C gene (NM_004187.5) using Whole exome sequencing (WES), highlighting the utility of this approach in identifying rare genetic disorders. The analysis also revealed the variable clinical features associated with KDM5C‐related disorders and identified missense variants as the most prevalent among the reported variants. Conclusions This study provides insights into the clinical and genetic characteristics of XLID associated with KDM5C gene mutations, highlighting the higher manifestation of seizures in males and also addressing the heterogeneity of phenotypes in females. It also identifies a novel pathogenic variant and emphasizes the importance of considering gender‐specific factors and further research to understand the underlying molecular mechanisms. CLINVAR Accession Number SCV004034082 |
| format | Article |
| id | doaj-art-ee2f47536a084cd5bc4e87fc52c36b21 |
| institution | Kabale University |
| issn | 2324-9269 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj-art-ee2f47536a084cd5bc4e87fc52c36b212025-01-24T08:16:42ZengWileyMolecular Genetics & Genomic Medicine2324-92692025-01-01131n/an/a10.1002/mgg3.70057Clinical Features and Genetic Characteristics of XLID Patients With KDM5C Gene Mutations: Insights on Phenotype–Genotype Correlations From 175 Previous Cases and Identification of a Novel VariantMohammad‐Reza Ghasemi0Zahra Esmaeilizadeh1Sahand Tehrani Fateh2Hossein Sadeghi3Saman Bagheri4Farzad Hashemi‐Gorji5Morteza Sheikhi Nooshabadi6Rasoul Madannezhad7Toktam Sadat Tavabe Ghavami8Reza Mirfakhraie9Mohammad Miryounesi10Department of Medical Genetics, Faculty of Medicine Shahid Beheshti University of Medical Sciences Tehran IranDepartment of Medical Genetics, Faculty of Medical Sciences Tarbiat Modares University Tehran IranSchool of Medicine Tehran University of Medical Sciences (TUMS) Tehran IranGenomic Research Center Shahid Beheshti University of Medical Sciences Tehran IranCenter for Comprehensive Genetic Services Shahid Beheshti University of Medical Sciences Tehran IranGenomic Research Center Shahid Beheshti University of Medical Sciences Tehran IranSchool of Medicine Shahid Beheshti University of Medical Sciences Tehran IranCenter for Comprehensive Genetic Services Shahid Beheshti University of Medical Sciences Tehran IranDepartment of Biology‐Genetics Islamic Azad University Science and Research Branch Tehran IranDepartment of Medical Genetics, Faculty of Medicine Shahid Beheshti University of Medical Sciences Tehran IranDepartment of Medical Genetics, Faculty of Medicine Shahid Beheshti University of Medical Sciences Tehran IranABSTRACT Background X‐linked intellectual disability (XLID) is a genetically heterogeneous disorder that results in cognitive impairment and developmental delays. Mutations in the KDM5C gene have been identified as a causative factor in XLID. This study aimed to identify novel variants associated with XLID and to investigate the clinical and genetic characteristics of XLID patients with mutations in the KDM5C gene. This study also conducted a narrative review of the literature to identify key clinical and genetic characteristics of XLID caused by mutations in the KDM5C gene. Study Design Whole‐exome sequencing was performed on the proband's DNA, and Sanger sequencing was used to confirm and analyze the identified variant in a 20‐month‐old male patient with motor and speech delays. Moreover, a comprehensive literature review was conducted to gather previously reported cases, providing insights into the molecular findings and clinical characteristics of this disorder. Results The study identified a novel variant, c.2704C>T:p.Gln902X, located in exon 19 of the KDM5C gene (NM_004187.5) using Whole exome sequencing (WES), highlighting the utility of this approach in identifying rare genetic disorders. The analysis also revealed the variable clinical features associated with KDM5C‐related disorders and identified missense variants as the most prevalent among the reported variants. Conclusions This study provides insights into the clinical and genetic characteristics of XLID associated with KDM5C gene mutations, highlighting the higher manifestation of seizures in males and also addressing the heterogeneity of phenotypes in females. It also identifies a novel pathogenic variant and emphasizes the importance of considering gender‐specific factors and further research to understand the underlying molecular mechanisms. CLINVAR Accession Number SCV004034082https://doi.org/10.1002/mgg3.70057KDM5Cnovel variantwhole exome sequencing (WES)X‐linked intellectual disability (XLID) |
| spellingShingle | Mohammad‐Reza Ghasemi Zahra Esmaeilizadeh Sahand Tehrani Fateh Hossein Sadeghi Saman Bagheri Farzad Hashemi‐Gorji Morteza Sheikhi Nooshabadi Rasoul Madannezhad Toktam Sadat Tavabe Ghavami Reza Mirfakhraie Mohammad Miryounesi Clinical Features and Genetic Characteristics of XLID Patients With KDM5C Gene Mutations: Insights on Phenotype–Genotype Correlations From 175 Previous Cases and Identification of a Novel Variant Molecular Genetics & Genomic Medicine KDM5C novel variant whole exome sequencing (WES) X‐linked intellectual disability (XLID) |
| title | Clinical Features and Genetic Characteristics of XLID Patients With KDM5C Gene Mutations: Insights on Phenotype–Genotype Correlations From 175 Previous Cases and Identification of a Novel Variant |
| title_full | Clinical Features and Genetic Characteristics of XLID Patients With KDM5C Gene Mutations: Insights on Phenotype–Genotype Correlations From 175 Previous Cases and Identification of a Novel Variant |
| title_fullStr | Clinical Features and Genetic Characteristics of XLID Patients With KDM5C Gene Mutations: Insights on Phenotype–Genotype Correlations From 175 Previous Cases and Identification of a Novel Variant |
| title_full_unstemmed | Clinical Features and Genetic Characteristics of XLID Patients With KDM5C Gene Mutations: Insights on Phenotype–Genotype Correlations From 175 Previous Cases and Identification of a Novel Variant |
| title_short | Clinical Features and Genetic Characteristics of XLID Patients With KDM5C Gene Mutations: Insights on Phenotype–Genotype Correlations From 175 Previous Cases and Identification of a Novel Variant |
| title_sort | clinical features and genetic characteristics of xlid patients with kdm5c gene mutations insights on phenotype genotype correlations from 175 previous cases and identification of a novel variant |
| topic | KDM5C novel variant whole exome sequencing (WES) X‐linked intellectual disability (XLID) |
| url | https://doi.org/10.1002/mgg3.70057 |
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