Deep clinical and genetic analysis of 17p13.3 region: 38 pediatric patients diagnosed using next-generation sequencing and literature review
Abstract Background Chromosome 17p13.3 is a region of genomic instability associated with different neurodevelopmental diseases. The malformation spectrum of 17p13.3 microdeletions ranges from an isolated lissencephaly sequence to Miller-Dieker syndrome, while 17p13.3 microduplications result in aut...
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BMC
2025-05-01
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| Series: | BMC Medical Genomics |
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| Online Access: | https://doi.org/10.1186/s12920-025-02155-y |
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| author | Xiaoshan Ji Qiong Xu Yulan Lu Bo Liu Feifan Xiao Qi Ni Suzhen Xu Renchao Liu Gang Li Bingbing Wu Shuizhen Zhou Huijun Wang |
| author_facet | Xiaoshan Ji Qiong Xu Yulan Lu Bo Liu Feifan Xiao Qi Ni Suzhen Xu Renchao Liu Gang Li Bingbing Wu Shuizhen Zhou Huijun Wang |
| author_sort | Xiaoshan Ji |
| collection | DOAJ |
| description | Abstract Background Chromosome 17p13.3 is a region of genomic instability associated with different neurodevelopmental diseases. The malformation spectrum of 17p13.3 microdeletions ranges from an isolated lissencephaly sequence to Miller-Dieker syndrome, while 17p13.3 microduplications result in autism, learning disabilities, microcephaly and other brain malformations. This study aims to provide a more comprehensive delineation of the clinical and genetic characteristics associated with 17p13.3 alterations. Methods We retrospectively analyzed the next-generation sequencing (NGS) data of more than 40 thousand patients from January 2016 to December 2021 and identified 38 pediatric patients with copy-number variations (CNVs) or single-nucleotide variations (SNVs) in 17p13.3 region. Published patients with CNVs in the 17p13.3 region were also collected and we performed a Chi-square test to compare the phenotype spectrum of microdeletions and microduplications. Results Among the 27 CNV patients, 20 patients with microdeletions and 7 patients with microduplications were found. PAFAH1B1 was the most frequently deleted gene and CRK was the most frequently duplicated gene. Affected genes in 11 SNV patients included PAFAH1B1 and PRPF8. Developmental delay was the most common abnormality detected in the 38 patients (29/38, 76.3%). Of note, Case 10 presented omphalocele and Case 23 presented scoliosis, webbed neck and bone cyst, all of which were unusual variant phenotypes in this region. The Chi-square test revealed that epilepsy, lissencephaly and short stature were statistically significant with microdeletions, while behavioral abnormalities and hand and foot abnormalities were significant with microduplications (p < 0.01). Conclusions While PAFAH1B1, YWHAE and CRK are associated with major phenotypes of 17p13.3, RTN4RL1 may be involved in white matter changes and HIC1 might contribute to the occurrence of omphalocele. This study provided a comprehensive understanding of genetic information and phenotype spectrum of the 17p13.3 region. |
| format | Article |
| id | doaj-art-9c8e25feb5a44344aec02f9978a7d138 |
| institution | DOAJ |
| issn | 1755-8794 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
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| series | BMC Medical Genomics |
| spelling | doaj-art-9c8e25feb5a44344aec02f9978a7d1382025-08-20T03:08:43ZengBMCBMC Medical Genomics1755-87942025-05-011811910.1186/s12920-025-02155-yDeep clinical and genetic analysis of 17p13.3 region: 38 pediatric patients diagnosed using next-generation sequencing and literature reviewXiaoshan Ji0Qiong Xu1Yulan Lu2Bo Liu3Feifan Xiao4Qi Ni5Suzhen Xu6Renchao Liu7Gang Li8Bingbing Wu9Shuizhen Zhou10Huijun Wang11Center for Molecular Medicine, Children’s Hospital of Fudan UniversityDepartment of Child Health Care, Children’s Hospital of Fudan UniversityCenter for Molecular Medicine, Children’s Hospital of Fudan UniversityCenter for Molecular Medicine, Children’s Hospital of Fudan UniversityCenter for Molecular Medicine, Children’s Hospital of Fudan UniversityDepartment of Neonatology, Children’s Hospital of Fudan UniversityCenter for Molecular Medicine, Children’s Hospital of Fudan UniversityCenter for Molecular Medicine, Children’s Hospital of Fudan UniversityCenter for Molecular Medicine, Children’s Hospital of Fudan UniversityCenter for Molecular Medicine, Children’s Hospital of Fudan UniversityDepartment of Neurology, Children’s Hospital of Fudan UniversityCenter for Molecular Medicine, Children’s Hospital of Fudan UniversityAbstract Background Chromosome 17p13.3 is a region of genomic instability associated with different neurodevelopmental diseases. The malformation spectrum of 17p13.3 microdeletions ranges from an isolated lissencephaly sequence to Miller-Dieker syndrome, while 17p13.3 microduplications result in autism, learning disabilities, microcephaly and other brain malformations. This study aims to provide a more comprehensive delineation of the clinical and genetic characteristics associated with 17p13.3 alterations. Methods We retrospectively analyzed the next-generation sequencing (NGS) data of more than 40 thousand patients from January 2016 to December 2021 and identified 38 pediatric patients with copy-number variations (CNVs) or single-nucleotide variations (SNVs) in 17p13.3 region. Published patients with CNVs in the 17p13.3 region were also collected and we performed a Chi-square test to compare the phenotype spectrum of microdeletions and microduplications. Results Among the 27 CNV patients, 20 patients with microdeletions and 7 patients with microduplications were found. PAFAH1B1 was the most frequently deleted gene and CRK was the most frequently duplicated gene. Affected genes in 11 SNV patients included PAFAH1B1 and PRPF8. Developmental delay was the most common abnormality detected in the 38 patients (29/38, 76.3%). Of note, Case 10 presented omphalocele and Case 23 presented scoliosis, webbed neck and bone cyst, all of which were unusual variant phenotypes in this region. The Chi-square test revealed that epilepsy, lissencephaly and short stature were statistically significant with microdeletions, while behavioral abnormalities and hand and foot abnormalities were significant with microduplications (p < 0.01). Conclusions While PAFAH1B1, YWHAE and CRK are associated with major phenotypes of 17p13.3, RTN4RL1 may be involved in white matter changes and HIC1 might contribute to the occurrence of omphalocele. This study provided a comprehensive understanding of genetic information and phenotype spectrum of the 17p13.3 region.https://doi.org/10.1186/s12920-025-02155-y17p13.3Copy number variantsSingle-nucleotide variationNext-generation sequencingLissencephalyDevelopmental delay |
| spellingShingle | Xiaoshan Ji Qiong Xu Yulan Lu Bo Liu Feifan Xiao Qi Ni Suzhen Xu Renchao Liu Gang Li Bingbing Wu Shuizhen Zhou Huijun Wang Deep clinical and genetic analysis of 17p13.3 region: 38 pediatric patients diagnosed using next-generation sequencing and literature review BMC Medical Genomics 17p13.3 Copy number variants Single-nucleotide variation Next-generation sequencing Lissencephaly Developmental delay |
| title | Deep clinical and genetic analysis of 17p13.3 region: 38 pediatric patients diagnosed using next-generation sequencing and literature review |
| title_full | Deep clinical and genetic analysis of 17p13.3 region: 38 pediatric patients diagnosed using next-generation sequencing and literature review |
| title_fullStr | Deep clinical and genetic analysis of 17p13.3 region: 38 pediatric patients diagnosed using next-generation sequencing and literature review |
| title_full_unstemmed | Deep clinical and genetic analysis of 17p13.3 region: 38 pediatric patients diagnosed using next-generation sequencing and literature review |
| title_short | Deep clinical and genetic analysis of 17p13.3 region: 38 pediatric patients diagnosed using next-generation sequencing and literature review |
| title_sort | deep clinical and genetic analysis of 17p13 3 region 38 pediatric patients diagnosed using next generation sequencing and literature review |
| topic | 17p13.3 Copy number variants Single-nucleotide variation Next-generation sequencing Lissencephaly Developmental delay |
| url | https://doi.org/10.1186/s12920-025-02155-y |
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