Clinical Characteristics, In Silico Analysis, and Intervention of Neonatal-Onset Inflammatory Bowel Disease With Combined Immunodeficiency Caused by Novel TTC7A Variants
We aimed to explore the genotypic and phenotypic characteristics of neonatal-onset inflammatory bowel disease (IBD) with combined immunodeficiency due to TTC7A mutation. We examined the clinical manifestations, imaging results, endoscopic and histological findings, interventions, and prognosis of a...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.921808/full |
| _version_ | 1811242585992200192 |
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| author | Yun-e Chen Jingfang Chen Wenxing Guo Yanhong Zhang Jialing Li Hui Xie Tong Shen Yunsheng Ge Yanru Huang Wenying Zheng Mei Lu |
| author_facet | Yun-e Chen Jingfang Chen Wenxing Guo Yanhong Zhang Jialing Li Hui Xie Tong Shen Yunsheng Ge Yanru Huang Wenying Zheng Mei Lu |
| author_sort | Yun-e Chen |
| collection | DOAJ |
| description | We aimed to explore the genotypic and phenotypic characteristics of neonatal-onset inflammatory bowel disease (IBD) with combined immunodeficiency due to TTC7A mutation. We examined the clinical manifestations, imaging results, endoscopic and histological findings, interventions, and prognosis of a proband with neonatal-onset IBD and performed biochemical analyses, whole-exome sequencing (WES), and in silico analysis. Our proband developed severe early-onset diarrhea, malnutrition, electrolyte imbalance, dehydration, and recurrent infections after birth. Radiographic and ultrasonic images showed no specific manifestations. Endoscopic and histological examination revealed chronic inflammation. Immune function examination indicated immunodeficiency. WES identified compound heterozygous TTC7A mutations (c.2355+4A>G, c.643G>T) in the proband. In the expression analysis, no abnormal splicing in the TTC7A sequence was observed due to the c.2355+4A>G mutation; however, the mRNA expression was reduced. The proband’s condition did not improve after treatment with methylprednisolone or leflunomide. The proband died when treatment was stopped at the age of 5 months and 19 days. Compound heterozygous mutations (c.2355+4A>G, c.643G>T) in the TTC7A gene are described and verified for the first time. Our report expands the phenotypic spectrum of TTC7A mutations and the genotypic spectrum of very early-onset IBD with combined immunodeficiency. |
| first_indexed | 2024-04-12T13:53:19Z |
| format | Article |
| id | doaj.art-b492a6bf2cfa454cac2cdc93f709ed21 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-12T13:53:19Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-b492a6bf2cfa454cac2cdc93f709ed212022-12-22T03:30:26ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-06-011310.3389/fgene.2022.921808921808Clinical Characteristics, In Silico Analysis, and Intervention of Neonatal-Onset Inflammatory Bowel Disease With Combined Immunodeficiency Caused by Novel TTC7A VariantsYun-e Chen0Jingfang Chen1Wenxing Guo2Yanhong Zhang3Jialing Li4Hui Xie5Tong Shen6Yunsheng Ge7Yanru Huang8Wenying Zheng9Mei Lu10Department of Pediatrics, Women and Children’s Hospital, School of Medicine, Xiamen University, Xiamen, ChinaDepartment of Gastroenterology, Xiamen Branch of the Children’s Hospital of Fudan University (Xiamen Children’s Hospital), Xiamen, ChinaDepartment of Pediatrics, Women and Children’s Hospital, School of Medicine, Xiamen University, Xiamen, ChinaDepartment of Ultrasound Medicine, Women and Children’s Hospital, School of Medicine, Xiamen University, Xiamen, ChinaDepartment of Gastroenterology, Xiamen Branch of the Children’s Hospital of Fudan University (Xiamen Children’s Hospital), Xiamen, ChinaDepartment of Pediatrics, Women and Children’s Hospital, School of Medicine, Xiamen University, Xiamen, ChinaDepartment of Pediatrics, Women and Children’s Hospital, School of Medicine, Xiamen University, Xiamen, ChinaPrenatal Diagnostic Center Laboratory, Women and Children’s Hospital, School of Medicine, Xiamen University, Xiamen, ChinaPrenatal Diagnostic Center Laboratory, Women and Children’s Hospital, School of Medicine, Xiamen University, Xiamen, ChinaGenokon Institute of Medical Science and Laboratory, Xiamen, ChinaDepartment of Pediatrics, Women and Children’s Hospital, School of Medicine, Xiamen University, Xiamen, ChinaWe aimed to explore the genotypic and phenotypic characteristics of neonatal-onset inflammatory bowel disease (IBD) with combined immunodeficiency due to TTC7A mutation. We examined the clinical manifestations, imaging results, endoscopic and histological findings, interventions, and prognosis of a proband with neonatal-onset IBD and performed biochemical analyses, whole-exome sequencing (WES), and in silico analysis. Our proband developed severe early-onset diarrhea, malnutrition, electrolyte imbalance, dehydration, and recurrent infections after birth. Radiographic and ultrasonic images showed no specific manifestations. Endoscopic and histological examination revealed chronic inflammation. Immune function examination indicated immunodeficiency. WES identified compound heterozygous TTC7A mutations (c.2355+4A>G, c.643G>T) in the proband. In the expression analysis, no abnormal splicing in the TTC7A sequence was observed due to the c.2355+4A>G mutation; however, the mRNA expression was reduced. The proband’s condition did not improve after treatment with methylprednisolone or leflunomide. The proband died when treatment was stopped at the age of 5 months and 19 days. Compound heterozygous mutations (c.2355+4A>G, c.643G>T) in the TTC7A gene are described and verified for the first time. Our report expands the phenotypic spectrum of TTC7A mutations and the genotypic spectrum of very early-onset IBD with combined immunodeficiency.https://www.frontiersin.org/articles/10.3389/fgene.2022.921808/fullinflammatory bowel diseaseimmunodeficiencyneonatalTTC7Aintervention |
| spellingShingle | Yun-e Chen Jingfang Chen Wenxing Guo Yanhong Zhang Jialing Li Hui Xie Tong Shen Yunsheng Ge Yanru Huang Wenying Zheng Mei Lu Clinical Characteristics, In Silico Analysis, and Intervention of Neonatal-Onset Inflammatory Bowel Disease With Combined Immunodeficiency Caused by Novel TTC7A Variants Frontiers in Genetics inflammatory bowel disease immunodeficiency neonatal TTC7A intervention |
| title | Clinical Characteristics, In Silico Analysis, and Intervention of Neonatal-Onset Inflammatory Bowel Disease With Combined Immunodeficiency Caused by Novel TTC7A Variants |
| title_full | Clinical Characteristics, In Silico Analysis, and Intervention of Neonatal-Onset Inflammatory Bowel Disease With Combined Immunodeficiency Caused by Novel TTC7A Variants |
| title_fullStr | Clinical Characteristics, In Silico Analysis, and Intervention of Neonatal-Onset Inflammatory Bowel Disease With Combined Immunodeficiency Caused by Novel TTC7A Variants |
| title_full_unstemmed | Clinical Characteristics, In Silico Analysis, and Intervention of Neonatal-Onset Inflammatory Bowel Disease With Combined Immunodeficiency Caused by Novel TTC7A Variants |
| title_short | Clinical Characteristics, In Silico Analysis, and Intervention of Neonatal-Onset Inflammatory Bowel Disease With Combined Immunodeficiency Caused by Novel TTC7A Variants |
| title_sort | clinical characteristics in silico analysis and intervention of neonatal onset inflammatory bowel disease with combined immunodeficiency caused by novel ttc7a variants |
| topic | inflammatory bowel disease immunodeficiency neonatal TTC7A intervention |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.921808/full |
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