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Case report: Identification of novel fibrillin-2 variants impacting disulfide bond and causing congenital contractural arachnodactyly

Background: Congenital contractural arachnodactyly (CCA) is an autosomal dominant connective tissue disorder with clinical features of arthrogryposis, arachnodactyly, crumpled ears, scoliosis, and muscular hypoplasia. The heterozygous pathogenic variants in FBN2 have been shown to cause CCA. Fibrill...

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Autores principales: Li, An-Lei, He, Ji-Qiang, Zeng, Lei, Hu, Yi-Qiao, Wang, Min, Long, Jie-Yi, Chang, Si-Hua, Jin, Jie-Yuan, Xiang, Rong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10020613/
https://www.ncbi.nlm.nih.gov/pubmed/36936417
http://dx.doi.org/10.3389/fgene.2023.1035887
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author Li, An-Lei
He, Ji-Qiang
Zeng, Lei
Hu, Yi-Qiao
Wang, Min
Long, Jie-Yi
Chang, Si-Hua
Jin, Jie-Yuan
Xiang, Rong
author_facet Li, An-Lei
He, Ji-Qiang
Zeng, Lei
Hu, Yi-Qiao
Wang, Min
Long, Jie-Yi
Chang, Si-Hua
Jin, Jie-Yuan
Xiang, Rong
author_sort Li, An-Lei
collection PubMed
description Background: Congenital contractural arachnodactyly (CCA) is an autosomal dominant connective tissue disorder with clinical features of arthrogryposis, arachnodactyly, crumpled ears, scoliosis, and muscular hypoplasia. The heterozygous pathogenic variants in FBN2 have been shown to cause CCA. Fibrillin-2 is related to the elasticity of the tissue and has been demonstrated to play an important role in the constitution of extracellular microfibrils in elastic fibers, providing strength and flexibility to the connective tissue that sustains the body’s joints and organs. Methods: We recruited two Chinese families with arachnodactyly and bilateral arthrogryposis of the fingers. Whole-exome sequencing (WES) and co-segregation analysis were employed to identify their genetic etiologies. Three-dimensional protein models were used to analyze the pathogenic mechanism of the identified variants. Results: We have reported two CCA families and identified two novel missense variants in FBN2 (NM_001999.3: c.4093T>C, p.C1365R and c.2384G>T, p.C795F). The structural models of the mutant FBN2 protein in rats exhibited that both the variants could break disulfide bonds. Conclusion: We detected two FBN2 variants in two families with CCA. Our description expands the genetic profile of CCA and emphasizes the pathogenicity of disulfide bond disruption in FBN2.
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spelling pubmed-100206132023-03-18 Case report: Identification of novel fibrillin-2 variants impacting disulfide bond and causing congenital contractural arachnodactyly Li, An-Lei He, Ji-Qiang Zeng, Lei Hu, Yi-Qiao Wang, Min Long, Jie-Yi Chang, Si-Hua Jin, Jie-Yuan Xiang, Rong Front Genet Genetics Background: Congenital contractural arachnodactyly (CCA) is an autosomal dominant connective tissue disorder with clinical features of arthrogryposis, arachnodactyly, crumpled ears, scoliosis, and muscular hypoplasia. The heterozygous pathogenic variants in FBN2 have been shown to cause CCA. Fibrillin-2 is related to the elasticity of the tissue and has been demonstrated to play an important role in the constitution of extracellular microfibrils in elastic fibers, providing strength and flexibility to the connective tissue that sustains the body’s joints and organs. Methods: We recruited two Chinese families with arachnodactyly and bilateral arthrogryposis of the fingers. Whole-exome sequencing (WES) and co-segregation analysis were employed to identify their genetic etiologies. Three-dimensional protein models were used to analyze the pathogenic mechanism of the identified variants. Results: We have reported two CCA families and identified two novel missense variants in FBN2 (NM_001999.3: c.4093T>C, p.C1365R and c.2384G>T, p.C795F). The structural models of the mutant FBN2 protein in rats exhibited that both the variants could break disulfide bonds. Conclusion: We detected two FBN2 variants in two families with CCA. Our description expands the genetic profile of CCA and emphasizes the pathogenicity of disulfide bond disruption in FBN2. Frontiers Media S.A. 2023-03-03 /pmc/articles/PMC10020613/ /pubmed/36936417 http://dx.doi.org/10.3389/fgene.2023.1035887 Text en Copyright © 2023 Li, He, Zeng, Hu, Wang, Long, Chang, Jin and Xiang. 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
Li, An-Lei
He, Ji-Qiang
Zeng, Lei
Hu, Yi-Qiao
Wang, Min
Long, Jie-Yi
Chang, Si-Hua
Jin, Jie-Yuan
Xiang, Rong
Case report: Identification of novel fibrillin-2 variants impacting disulfide bond and causing congenital contractural arachnodactyly
title Case report: Identification of novel fibrillin-2 variants impacting disulfide bond and causing congenital contractural arachnodactyly
title_full Case report: Identification of novel fibrillin-2 variants impacting disulfide bond and causing congenital contractural arachnodactyly
title_fullStr Case report: Identification of novel fibrillin-2 variants impacting disulfide bond and causing congenital contractural arachnodactyly
title_full_unstemmed Case report: Identification of novel fibrillin-2 variants impacting disulfide bond and causing congenital contractural arachnodactyly
title_short Case report: Identification of novel fibrillin-2 variants impacting disulfide bond and causing congenital contractural arachnodactyly
title_sort case report: identification of novel fibrillin-2 variants impacting disulfide bond and causing congenital contractural arachnodactyly
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10020613/
https://www.ncbi.nlm.nih.gov/pubmed/36936417
http://dx.doi.org/10.3389/fgene.2023.1035887
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