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A synonymous mutation in PI4KA impacts the transcription and translation process of gene expression
Phosphatidylinositol-4-kinase alpha (PI4KIIIα), encoded by the PI4KA gene, can synthesize phosphatidylinositol-4-phosphate (PI-4-P), which serves as a specific membrane marker and is instrumental in signal transduction. PI4KA mutations can cause autosomal recessive diseases involving neurological, i...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9627211/ https://www.ncbi.nlm.nih.gov/pubmed/36341355 http://dx.doi.org/10.3389/fimmu.2022.987666 |
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author | Zhang, Kaihui Kang, Lili Zhang, Haozheng Bai, Lu Pang, Huanping Liu, Qinghua Zhang, Xinyi Chen, Dong Yu, Haihua Lv, Yuqiang Gao, Min Liu, Yi Gai, Zhongtao Wang, Dong Li, Xiaoying |
author_facet | Zhang, Kaihui Kang, Lili Zhang, Haozheng Bai, Lu Pang, Huanping Liu, Qinghua Zhang, Xinyi Chen, Dong Yu, Haihua Lv, Yuqiang Gao, Min Liu, Yi Gai, Zhongtao Wang, Dong Li, Xiaoying |
author_sort | Zhang, Kaihui |
collection | PubMed |
description | Phosphatidylinositol-4-kinase alpha (PI4KIIIα), encoded by the PI4KA gene, can synthesize phosphatidylinositol-4-phosphate (PI-4-P), which serves as a specific membrane marker and is instrumental in signal transduction. PI4KA mutations can cause autosomal recessive diseases involving neurological, intestinal, and immunological conditions (OMIM:619621, 616531, 619708). We detected sepsis, severe diarrhea, and decreased immunoglobulin levels in one neonate. Two novel compound heterozygous mutations, c.5846T>C (p.Leu1949Pro) and c.3453C>T (p.Gly1151=), were identified in the neonate from the father and the mother, respectively. Sanger sequencing and reverse transcription polymerase chain reaction (RT-PCR) for peripheral blood and minigene splicing assays showed a deletion of five bases (GTGAG) with the c.3453C>T variant at the mRNA level, which could result in a truncated protein (p.Gly1151GlyfsTer17). The missense mutation c.5846T>C (p.Leu1949Pro) kinase activity was measured, and little or no catalytic activity was detected. According to the clinical characteristics and gene mutations with functional verification, our pediatricians diagnosed the child with a combined immunodeficiency and intestinal disorder close to gastrointestinal defects and immunodeficiency syndrome 2 (GIDID2; OMIM: 619708). Medicines such as immunomodulators are prescribed to balance immune dysregulation. This study is the first report of a synonymous mutation in the PI4KA gene that influences alternative splicing. Our findings expand the mutation spectrum leading to PI4KIIIa deficiency-related diseases and provide exact information for genetic counseling. |
format | Online Article Text |
id | pubmed-9627211 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-96272112022-11-03 A synonymous mutation in PI4KA impacts the transcription and translation process of gene expression Zhang, Kaihui Kang, Lili Zhang, Haozheng Bai, Lu Pang, Huanping Liu, Qinghua Zhang, Xinyi Chen, Dong Yu, Haihua Lv, Yuqiang Gao, Min Liu, Yi Gai, Zhongtao Wang, Dong Li, Xiaoying Front Immunol Immunology Phosphatidylinositol-4-kinase alpha (PI4KIIIα), encoded by the PI4KA gene, can synthesize phosphatidylinositol-4-phosphate (PI-4-P), which serves as a specific membrane marker and is instrumental in signal transduction. PI4KA mutations can cause autosomal recessive diseases involving neurological, intestinal, and immunological conditions (OMIM:619621, 616531, 619708). We detected sepsis, severe diarrhea, and decreased immunoglobulin levels in one neonate. Two novel compound heterozygous mutations, c.5846T>C (p.Leu1949Pro) and c.3453C>T (p.Gly1151=), were identified in the neonate from the father and the mother, respectively. Sanger sequencing and reverse transcription polymerase chain reaction (RT-PCR) for peripheral blood and minigene splicing assays showed a deletion of five bases (GTGAG) with the c.3453C>T variant at the mRNA level, which could result in a truncated protein (p.Gly1151GlyfsTer17). The missense mutation c.5846T>C (p.Leu1949Pro) kinase activity was measured, and little or no catalytic activity was detected. According to the clinical characteristics and gene mutations with functional verification, our pediatricians diagnosed the child with a combined immunodeficiency and intestinal disorder close to gastrointestinal defects and immunodeficiency syndrome 2 (GIDID2; OMIM: 619708). Medicines such as immunomodulators are prescribed to balance immune dysregulation. This study is the first report of a synonymous mutation in the PI4KA gene that influences alternative splicing. Our findings expand the mutation spectrum leading to PI4KIIIa deficiency-related diseases and provide exact information for genetic counseling. Frontiers Media S.A. 2022-10-19 /pmc/articles/PMC9627211/ /pubmed/36341355 http://dx.doi.org/10.3389/fimmu.2022.987666 Text en Copyright © 2022 Zhang, Kang, Zhang, Bai, Pang, Liu, Zhang, Chen, Yu, Lv, Gao, Liu, Gai, Wang and Li 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 | Immunology Zhang, Kaihui Kang, Lili Zhang, Haozheng Bai, Lu Pang, Huanping Liu, Qinghua Zhang, Xinyi Chen, Dong Yu, Haihua Lv, Yuqiang Gao, Min Liu, Yi Gai, Zhongtao Wang, Dong Li, Xiaoying A synonymous mutation in PI4KA impacts the transcription and translation process of gene expression |
title | A synonymous mutation in PI4KA impacts the transcription and translation process of gene expression |
title_full | A synonymous mutation in PI4KA impacts the transcription and translation process of gene expression |
title_fullStr | A synonymous mutation in PI4KA impacts the transcription and translation process of gene expression |
title_full_unstemmed | A synonymous mutation in PI4KA impacts the transcription and translation process of gene expression |
title_short | A synonymous mutation in PI4KA impacts the transcription and translation process of gene expression |
title_sort | synonymous mutation in pi4ka impacts the transcription and translation process of gene expression |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9627211/ https://www.ncbi.nlm.nih.gov/pubmed/36341355 http://dx.doi.org/10.3389/fimmu.2022.987666 |
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