Novel Compound Heterozygous Variants in ZNF526 Causing Dentici‐Novelli Neurodevelopmental Syndrome: A Case Report and Literature Review
ABSTRACT Background The ZNF526 gene encodes a ubiquitously expressed Kruppel‐type zinc finger protein crucial in transcriptional regulation. Recent studies suggest that biallelic pathogenic variants in ZNF526 may lead to Dentici‐Novelli neurodevelopmental syndrome, characterized by microcephaly, dev...
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| Format: | Article |
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Wiley
2025-04-01
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| Series: | Molecular Genetics & Genomic Medicine |
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| Online Access: | https://doi.org/10.1002/mgg3.70089 |
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| author | Shaoxin Li Hui Fang Hong Li Min Peng Jinsong Bao Yunfei Cai Jing Chen Zhige Li |
| author_facet | Shaoxin Li Hui Fang Hong Li Min Peng Jinsong Bao Yunfei Cai Jing Chen Zhige Li |
| author_sort | Shaoxin Li |
| collection | DOAJ |
| description | ABSTRACT Background The ZNF526 gene encodes a ubiquitously expressed Kruppel‐type zinc finger protein crucial in transcriptional regulation. Recent studies suggest that biallelic pathogenic variants in ZNF526 may lead to Dentici‐Novelli neurodevelopmental syndrome, characterized by microcephaly, developmental delay, epilepsy, and ocular anomalies. To date, phenotypic details have been reported for only six patients with ZNF526 variants. Methods This study gathered clinical information and genetic data from a child with neurodevelopmental disorders. A three‐dimensional protein model was employed to predict variant effects on protein structure. A literature review was conducted to compare this case with previously reported cases, analyzing clinical features and genetic findings. Results The proband, a 7‐month‐old girl, exhibited developmental delay, microcephaly, limb hypotonia, abnormal brain imaging, and seizures. Chromosomal karyotype analysis and copy number variation analyses were normal. Whole exome sequencing revealed two heterozygous variants in the ZNF526 gene (NM_133444.3): c.1426del (p.Val476Phefs*9), a de novo frameshift variant, and c.1513T;> C (p.Cys505Arg), inherited from her mother. These previously unreported variants are on separate alleles, forming a compound heterozygous state correlated with the clinical presentation. Ocular anomalies were absent, while café‐au‐lait spots may represent a novel feature. Among 12 cases of Dentici‐Novelli neurodevelopmental syndrome, 11 unique ZNF526 variants have been identified, with loss‐of‐function variants possibly linked to seizures. Conclusion This study describes the youngest patient with Dentici‐Novelli neurodevelopmental syndrome, broadening the ZNF526 mutation spectrum and detailing the associated clinical profile. These findings are valuable for genetic diagnosis and family counseling in cases of this syndrome. |
| format | Article |
| id | doaj-art-be2a1c2401814ddb8a87522efbb2e671 |
| institution | OA Journals |
| issn | 2324-9269 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Wiley |
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| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj-art-be2a1c2401814ddb8a87522efbb2e6712025-08-20T01:50:57ZengWileyMolecular Genetics & Genomic Medicine2324-92692025-04-01134n/an/a10.1002/mgg3.70089Novel Compound Heterozygous Variants in ZNF526 Causing Dentici‐Novelli Neurodevelopmental Syndrome: A Case Report and Literature ReviewShaoxin Li0Hui Fang1Hong Li2Min Peng3Jinsong Bao4Yunfei Cai5Jing Chen6Zhige Li7Department of Rehabilitation Anhui Provincial Children's Hospital Hefei ChinaDepartment of Rehabilitation Anhui Provincial Children's Hospital Hefei ChinaDepartment of Rehabilitation Anhui Provincial Children's Hospital Hefei ChinaChigene (Beijing) Translational Medical Research Center Co. Beijing ChinaDepartment of Rehabilitation Anhui Provincial Children's Hospital Hefei ChinaDepartment of Rehabilitation Anhui Provincial Children's Hospital Hefei ChinaDepartment of Rehabilitation Anhui Provincial Children's Hospital Hefei ChinaDepartment of Rehabilitation Anhui Provincial Children's Hospital Hefei ChinaABSTRACT Background The ZNF526 gene encodes a ubiquitously expressed Kruppel‐type zinc finger protein crucial in transcriptional regulation. Recent studies suggest that biallelic pathogenic variants in ZNF526 may lead to Dentici‐Novelli neurodevelopmental syndrome, characterized by microcephaly, developmental delay, epilepsy, and ocular anomalies. To date, phenotypic details have been reported for only six patients with ZNF526 variants. Methods This study gathered clinical information and genetic data from a child with neurodevelopmental disorders. A three‐dimensional protein model was employed to predict variant effects on protein structure. A literature review was conducted to compare this case with previously reported cases, analyzing clinical features and genetic findings. Results The proband, a 7‐month‐old girl, exhibited developmental delay, microcephaly, limb hypotonia, abnormal brain imaging, and seizures. Chromosomal karyotype analysis and copy number variation analyses were normal. Whole exome sequencing revealed two heterozygous variants in the ZNF526 gene (NM_133444.3): c.1426del (p.Val476Phefs*9), a de novo frameshift variant, and c.1513T;> C (p.Cys505Arg), inherited from her mother. These previously unreported variants are on separate alleles, forming a compound heterozygous state correlated with the clinical presentation. Ocular anomalies were absent, while café‐au‐lait spots may represent a novel feature. Among 12 cases of Dentici‐Novelli neurodevelopmental syndrome, 11 unique ZNF526 variants have been identified, with loss‐of‐function variants possibly linked to seizures. Conclusion This study describes the youngest patient with Dentici‐Novelli neurodevelopmental syndrome, broadening the ZNF526 mutation spectrum and detailing the associated clinical profile. These findings are valuable for genetic diagnosis and family counseling in cases of this syndrome.https://doi.org/10.1002/mgg3.70089Dentici‐Novelli neurodevelopmental syndromeglobal developmental delaymicrocephalyneurodevelopmental disorderZNF526 gene |
| spellingShingle | Shaoxin Li Hui Fang Hong Li Min Peng Jinsong Bao Yunfei Cai Jing Chen Zhige Li Novel Compound Heterozygous Variants in ZNF526 Causing Dentici‐Novelli Neurodevelopmental Syndrome: A Case Report and Literature Review Molecular Genetics & Genomic Medicine Dentici‐Novelli neurodevelopmental syndrome global developmental delay microcephaly neurodevelopmental disorder ZNF526 gene |
| title | Novel Compound Heterozygous Variants in ZNF526 Causing Dentici‐Novelli Neurodevelopmental Syndrome: A Case Report and Literature Review |
| title_full | Novel Compound Heterozygous Variants in ZNF526 Causing Dentici‐Novelli Neurodevelopmental Syndrome: A Case Report and Literature Review |
| title_fullStr | Novel Compound Heterozygous Variants in ZNF526 Causing Dentici‐Novelli Neurodevelopmental Syndrome: A Case Report and Literature Review |
| title_full_unstemmed | Novel Compound Heterozygous Variants in ZNF526 Causing Dentici‐Novelli Neurodevelopmental Syndrome: A Case Report and Literature Review |
| title_short | Novel Compound Heterozygous Variants in ZNF526 Causing Dentici‐Novelli Neurodevelopmental Syndrome: A Case Report and Literature Review |
| title_sort | novel compound heterozygous variants in znf526 causing dentici novelli neurodevelopmental syndrome a case report and literature review |
| topic | Dentici‐Novelli neurodevelopmental syndrome global developmental delay microcephaly neurodevelopmental disorder ZNF526 gene |
| url | https://doi.org/10.1002/mgg3.70089 |
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