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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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Autores principales: Chen, Yun-e, Chen, Jingfang, Guo, Wenxing, Zhang, Yanhong, Li, Jialing, Xie, Hui, Shen, Tong, Ge, Yunsheng, Huang, Yanru, Zheng, Wenying, Lu, Mei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9243236/
https://www.ncbi.nlm.nih.gov/pubmed/35783276
http://dx.doi.org/10.3389/fgene.2022.921808
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author Chen, Yun-e
Chen, Jingfang
Guo, Wenxing
Zhang, Yanhong
Li, Jialing
Xie, Hui
Shen, Tong
Ge, Yunsheng
Huang, Yanru
Zheng, Wenying
Lu, Mei
author_facet Chen, Yun-e
Chen, Jingfang
Guo, Wenxing
Zhang, Yanhong
Li, Jialing
Xie, Hui
Shen, Tong
Ge, Yunsheng
Huang, Yanru
Zheng, Wenying
Lu, Mei
author_sort Chen, Yun-e
collection PubMed
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.
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spelling pubmed-92432362022-07-01 Clinical Characteristics, In Silico Analysis, and Intervention of Neonatal-Onset Inflammatory Bowel Disease With Combined Immunodeficiency Caused by Novel TTC7A Variants Chen, Yun-e Chen, Jingfang Guo, Wenxing Zhang, Yanhong Li, Jialing Xie, Hui Shen, Tong Ge, Yunsheng Huang, Yanru Zheng, Wenying Lu, Mei Front Genet Genetics 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. Frontiers Media S.A. 2022-06-16 /pmc/articles/PMC9243236/ /pubmed/35783276 http://dx.doi.org/10.3389/fgene.2022.921808 Text en Copyright © 2022 Chen, Chen, Guo, Zhang, Li, Xie, Shen, Ge, Huang, Zheng and Lu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Chen, Yun-e
Chen, Jingfang
Guo, Wenxing
Zhang, Yanhong
Li, Jialing
Xie, Hui
Shen, Tong
Ge, Yunsheng
Huang, Yanru
Zheng, Wenying
Lu, Mei
Clinical Characteristics, In Silico Analysis, and Intervention of Neonatal-Onset Inflammatory Bowel Disease With Combined Immunodeficiency Caused by Novel TTC7A Variants
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 Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9243236/
https://www.ncbi.nlm.nih.gov/pubmed/35783276
http://dx.doi.org/10.3389/fgene.2022.921808
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