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Case Report: Identification and Functional Analysis of a Homozygous Synonymous Variant in the PLOD1 Gene in a Chinese Neonatal With the Ehlers–Danlos Syndrome

BACKGROUND: Kyphoscoliotic Ehlers–Danlos syndrome (kEDS; OMIM225400) is a rare autosomal recessive genetic disease caused by variants in the PLOD1 gene. This research was conducted to verify the disease-causing gene in a Chinese neonatal family with the EDS. METHODS: We recruited a Han Chinese neona...

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Autores principales: Yan, Xiaodan, Shu, Jianbo, Nie, Yanyan, Zhang, Ying, Wang, Ping, Zhou, Weiwei, Cui, Xiaoyu, Liu, Yang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8891444/
https://www.ncbi.nlm.nih.gov/pubmed/35252061
http://dx.doi.org/10.3389/fped.2022.813758
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author Yan, Xiaodan
Shu, Jianbo
Nie, Yanyan
Zhang, Ying
Wang, Ping
Zhou, Weiwei
Cui, Xiaoyu
Liu, Yang
author_facet Yan, Xiaodan
Shu, Jianbo
Nie, Yanyan
Zhang, Ying
Wang, Ping
Zhou, Weiwei
Cui, Xiaoyu
Liu, Yang
author_sort Yan, Xiaodan
collection PubMed
description BACKGROUND: Kyphoscoliotic Ehlers–Danlos syndrome (kEDS; OMIM225400) is a rare autosomal recessive genetic disease caused by variants in the PLOD1 gene. This research was conducted to verify the disease-causing gene in a Chinese neonatal family with the EDS. METHODS: We recruited a Han Chinese neonate with PLOD1-related kEDS without kyphoscoliosis. Detailed clinical examination and laboratory tests were performed and whole exome sequencing (WES) was used to detect the pathogenic genes of the proband. In vivo experiments (reverse-transcription PCR, quantitative real-time PCR) and in vitro experiments (minigene analysis) were used to verify the function of variants suspected of affecting the splicing process. The effect of the splice site variant on the PLOD1 transcript was analyzed using splice prediction programs NetGene2 and Alternative Splice Site Predictor (ASSP). RESULTS: A homozygous synonymous variant c.1095C>T (p.Gly365, rs1032781250) in the PLOD1 gene was found and verified in the family with kEDS. This splicing variant resulted in a premature termination codon of exon 10 and affected the expression of the four bases GCGC. CONCLUSION: Our research showed that the homozygous synonymous variant in PLOD1 was the pathogenic cause in the proband. The combined application of WES and functional studies verified the effect of uncertain gene variants on splicing, upgrading pathogenicity evidence, and determining the cause of disease. This is helpful for the early diagnosis and treatment of kEDS.
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spelling pubmed-88914442022-03-04 Case Report: Identification and Functional Analysis of a Homozygous Synonymous Variant in the PLOD1 Gene in a Chinese Neonatal With the Ehlers–Danlos Syndrome Yan, Xiaodan Shu, Jianbo Nie, Yanyan Zhang, Ying Wang, Ping Zhou, Weiwei Cui, Xiaoyu Liu, Yang Front Pediatr Pediatrics BACKGROUND: Kyphoscoliotic Ehlers–Danlos syndrome (kEDS; OMIM225400) is a rare autosomal recessive genetic disease caused by variants in the PLOD1 gene. This research was conducted to verify the disease-causing gene in a Chinese neonatal family with the EDS. METHODS: We recruited a Han Chinese neonate with PLOD1-related kEDS without kyphoscoliosis. Detailed clinical examination and laboratory tests were performed and whole exome sequencing (WES) was used to detect the pathogenic genes of the proband. In vivo experiments (reverse-transcription PCR, quantitative real-time PCR) and in vitro experiments (minigene analysis) were used to verify the function of variants suspected of affecting the splicing process. The effect of the splice site variant on the PLOD1 transcript was analyzed using splice prediction programs NetGene2 and Alternative Splice Site Predictor (ASSP). RESULTS: A homozygous synonymous variant c.1095C>T (p.Gly365, rs1032781250) in the PLOD1 gene was found and verified in the family with kEDS. This splicing variant resulted in a premature termination codon of exon 10 and affected the expression of the four bases GCGC. CONCLUSION: Our research showed that the homozygous synonymous variant in PLOD1 was the pathogenic cause in the proband. The combined application of WES and functional studies verified the effect of uncertain gene variants on splicing, upgrading pathogenicity evidence, and determining the cause of disease. This is helpful for the early diagnosis and treatment of kEDS. Frontiers Media S.A. 2022-02-17 /pmc/articles/PMC8891444/ /pubmed/35252061 http://dx.doi.org/10.3389/fped.2022.813758 Text en Copyright © 2022 Yan, Shu, Nie, Zhang, Wang, Zhou, Cui and Liu. 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 Pediatrics
Yan, Xiaodan
Shu, Jianbo
Nie, Yanyan
Zhang, Ying
Wang, Ping
Zhou, Weiwei
Cui, Xiaoyu
Liu, Yang
Case Report: Identification and Functional Analysis of a Homozygous Synonymous Variant in the PLOD1 Gene in a Chinese Neonatal With the Ehlers–Danlos Syndrome
title Case Report: Identification and Functional Analysis of a Homozygous Synonymous Variant in the PLOD1 Gene in a Chinese Neonatal With the Ehlers–Danlos Syndrome
title_full Case Report: Identification and Functional Analysis of a Homozygous Synonymous Variant in the PLOD1 Gene in a Chinese Neonatal With the Ehlers–Danlos Syndrome
title_fullStr Case Report: Identification and Functional Analysis of a Homozygous Synonymous Variant in the PLOD1 Gene in a Chinese Neonatal With the Ehlers–Danlos Syndrome
title_full_unstemmed Case Report: Identification and Functional Analysis of a Homozygous Synonymous Variant in the PLOD1 Gene in a Chinese Neonatal With the Ehlers–Danlos Syndrome
title_short Case Report: Identification and Functional Analysis of a Homozygous Synonymous Variant in the PLOD1 Gene in a Chinese Neonatal With the Ehlers–Danlos Syndrome
title_sort case report: identification and functional analysis of a homozygous synonymous variant in the plod1 gene in a chinese neonatal with the ehlers–danlos syndrome
topic Pediatrics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8891444/
https://www.ncbi.nlm.nih.gov/pubmed/35252061
http://dx.doi.org/10.3389/fped.2022.813758
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