The Expanding Phenotype of ZTTK Syndrome Due to the Heterozygous Variant of <i>SON</i> Gene Focusing on Liver Involvement: Patient Report and Literature Review
Zhu–Tokita–Takenouchi–Kim (ZTTK) syndrome, an intellectual disability syndrome first described in 2016, is caused by heterozygous loss-of-function variants in <i>SON</i>. Haploinsufficiency in <i>SON</i> may affect multiple genes, including those involved in the development a...
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MDPI AG
2023-03-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/14/3/739 |
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| author | Andrea Pietrobattista Luca Della Volpe Paola Francalanci Lorenzo Figà Talamanca Lidia Monti Francesca Romana Lepri Maria Sole Basso Daniela Liccardo Claudia Della Corte Antonella Mosca Tommaso Alterio Silvio Veraldi Francesco Callea Antonio Novelli Giuseppe Maggiore |
| author_facet | Andrea Pietrobattista Luca Della Volpe Paola Francalanci Lorenzo Figà Talamanca Lidia Monti Francesca Romana Lepri Maria Sole Basso Daniela Liccardo Claudia Della Corte Antonella Mosca Tommaso Alterio Silvio Veraldi Francesco Callea Antonio Novelli Giuseppe Maggiore |
| author_sort | Andrea Pietrobattista |
| collection | DOAJ |
| description | Zhu–Tokita–Takenouchi–Kim (ZTTK) syndrome, an intellectual disability syndrome first described in 2016, is caused by heterozygous loss-of-function variants in <i>SON</i>. Haploinsufficiency in <i>SON</i> may affect multiple genes, including those involved in the development and metabolism of multiple organs. Considering the broad spectrum of <i>SON</i> functions, it is to be expected that pathogenic variants in this gene can cause a wide spectrum of clinical symptoms. We present an additional ZTTK syndrome case due to a de novo heterozygous variant in the <i>SON</i> gene (<i>c.5751_5754delAGTT</i>). The clinical manifestations of our patient were similar to those present in previously reported cases; however, the diagnosis of ZTTK syndrome was delayed for a long time and was carried out during the diagnostic work-up of significant chronic liver disease (CLD). CLD has not yet been reported in any series; therefore, our report provides new information on this rare condition and suggests the expansion of the ZTTK syndrome phenotype, including possible liver involvement. Correspondingly, we recommend screening patients with <i>SON</i> variants specifically for liver involvement from the first years of life. Once the CLD has been diagnosed, an appropriate follow-up is mandatory, especially considering the role of <i>SON</i> as an emerging player in cancer development. Further studies are needed to investigate the role of <i>SON</i> haploinsufficiency as a downregulator of essential genes, thus potentially impairing the normal development and/or functions of multiple organs. |
| first_indexed | 2024-03-11T06:29:28Z |
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| id | doaj.art-cc8459ed6cce443fb3dca8bbe55b4ff8 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-11T06:29:28Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-cc8459ed6cce443fb3dca8bbe55b4ff82023-11-17T11:18:46ZengMDPI AGGenes2073-44252023-03-0114373910.3390/genes14030739The Expanding Phenotype of ZTTK Syndrome Due to the Heterozygous Variant of <i>SON</i> Gene Focusing on Liver Involvement: Patient Report and Literature ReviewAndrea Pietrobattista0Luca Della Volpe1Paola Francalanci2Lorenzo Figà Talamanca3Lidia Monti4Francesca Romana Lepri5Maria Sole Basso6Daniela Liccardo7Claudia Della Corte8Antonella Mosca9Tommaso Alterio10Silvio Veraldi11Francesco Callea12Antonio Novelli13Giuseppe Maggiore14Hepatogastroenterology, Nutrition, Digestive Endoscopy and Liver Transplant Unit, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, ItalyHepatogastroenterology, Nutrition, Digestive Endoscopy and Liver Transplant Unit, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, ItalyPathology Unit, Department of Diagnostic and Laboratory Medicine, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, ItalyDepartment of Radiology, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, ItalyDepartment of Radiology, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, ItalyLaboratory of Medical Genetics, Translational Cytogenomics Research Unity, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, ItalyHepatogastroenterology, Nutrition, Digestive Endoscopy and Liver Transplant Unit, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, ItalyHepatogastroenterology, Nutrition, Digestive Endoscopy and Liver Transplant Unit, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, ItalyHepatogastroenterology, Nutrition, Digestive Endoscopy and Liver Transplant Unit, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, ItalyHepatogastroenterology, Nutrition, Digestive Endoscopy and Liver Transplant Unit, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, ItalyHepatogastroenterology, Nutrition, Digestive Endoscopy and Liver Transplant Unit, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, ItalyHepatogastroenterology, Nutrition, Digestive Endoscopy and Liver Transplant Unit, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, ItalyDepartment of Histopathology, Bugando Medical Centre, Catholic University of Healthy Allied Sciences, Mwanza P.O. Box 1370, TanzaniaLaboratory of Medical Genetics, Translational Cytogenomics Research Unity, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, ItalyHepatogastroenterology, Nutrition, Digestive Endoscopy and Liver Transplant Unit, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, ItalyZhu–Tokita–Takenouchi–Kim (ZTTK) syndrome, an intellectual disability syndrome first described in 2016, is caused by heterozygous loss-of-function variants in <i>SON</i>. Haploinsufficiency in <i>SON</i> may affect multiple genes, including those involved in the development and metabolism of multiple organs. Considering the broad spectrum of <i>SON</i> functions, it is to be expected that pathogenic variants in this gene can cause a wide spectrum of clinical symptoms. We present an additional ZTTK syndrome case due to a de novo heterozygous variant in the <i>SON</i> gene (<i>c.5751_5754delAGTT</i>). The clinical manifestations of our patient were similar to those present in previously reported cases; however, the diagnosis of ZTTK syndrome was delayed for a long time and was carried out during the diagnostic work-up of significant chronic liver disease (CLD). CLD has not yet been reported in any series; therefore, our report provides new information on this rare condition and suggests the expansion of the ZTTK syndrome phenotype, including possible liver involvement. Correspondingly, we recommend screening patients with <i>SON</i> variants specifically for liver involvement from the first years of life. Once the CLD has been diagnosed, an appropriate follow-up is mandatory, especially considering the role of <i>SON</i> as an emerging player in cancer development. Further studies are needed to investigate the role of <i>SON</i> haploinsufficiency as a downregulator of essential genes, thus potentially impairing the normal development and/or functions of multiple organs.https://www.mdpi.com/2073-4425/14/3/739chronic liver diseaseZTTK syndrome<i>SON</i> mutationbrain malformationsdevelopmental delay |
| spellingShingle | Andrea Pietrobattista Luca Della Volpe Paola Francalanci Lorenzo Figà Talamanca Lidia Monti Francesca Romana Lepri Maria Sole Basso Daniela Liccardo Claudia Della Corte Antonella Mosca Tommaso Alterio Silvio Veraldi Francesco Callea Antonio Novelli Giuseppe Maggiore The Expanding Phenotype of ZTTK Syndrome Due to the Heterozygous Variant of <i>SON</i> Gene Focusing on Liver Involvement: Patient Report and Literature Review Genes chronic liver disease ZTTK syndrome <i>SON</i> mutation brain malformations developmental delay |
| title | The Expanding Phenotype of ZTTK Syndrome Due to the Heterozygous Variant of <i>SON</i> Gene Focusing on Liver Involvement: Patient Report and Literature Review |
| title_full | The Expanding Phenotype of ZTTK Syndrome Due to the Heterozygous Variant of <i>SON</i> Gene Focusing on Liver Involvement: Patient Report and Literature Review |
| title_fullStr | The Expanding Phenotype of ZTTK Syndrome Due to the Heterozygous Variant of <i>SON</i> Gene Focusing on Liver Involvement: Patient Report and Literature Review |
| title_full_unstemmed | The Expanding Phenotype of ZTTK Syndrome Due to the Heterozygous Variant of <i>SON</i> Gene Focusing on Liver Involvement: Patient Report and Literature Review |
| title_short | The Expanding Phenotype of ZTTK Syndrome Due to the Heterozygous Variant of <i>SON</i> Gene Focusing on Liver Involvement: Patient Report and Literature Review |
| title_sort | expanding phenotype of zttk syndrome due to the heterozygous variant of i son i gene focusing on liver involvement patient report and literature review |
| topic | chronic liver disease ZTTK syndrome <i>SON</i> mutation brain malformations developmental delay |
| url | https://www.mdpi.com/2073-4425/14/3/739 |
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