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A novel variant of IHH in a Chinese family with brachydactyly type 1

BACKGROUND: Brachydactyly type A1(BDA-1) is an autosomal dominant disorder which is caused by heterozygous pathogenic variants in a specific region of the N-terminal active fragment of Indian Hedgehog (IHH). The disorder is mainly characterized by shortening or missing of the middle phalanges. In th...

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Autores principales: Yang, Qi, Wang, Jin, Tian, Xiaoxian, Shen, Fei, Lan, Jing, Zhang, Qiang, Fan, Xin, Yi, Shang, Li, Mengting, Shen, Yiping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7092535/
https://www.ncbi.nlm.nih.gov/pubmed/32209048
http://dx.doi.org/10.1186/s12881-020-01000-6
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author Yang, Qi
Wang, Jin
Tian, Xiaoxian
Shen, Fei
Lan, Jing
Zhang, Qiang
Fan, Xin
Yi, Shang
Li, Mengting
Shen, Yiping
author_facet Yang, Qi
Wang, Jin
Tian, Xiaoxian
Shen, Fei
Lan, Jing
Zhang, Qiang
Fan, Xin
Yi, Shang
Li, Mengting
Shen, Yiping
author_sort Yang, Qi
collection PubMed
description BACKGROUND: Brachydactyly type A1(BDA-1) is an autosomal dominant disorder which is caused by heterozygous pathogenic variants in a specific region of the N-terminal active fragment of Indian Hedgehog (IHH). The disorder is mainly characterized by shortening or missing of the middle phalanges. In this study, Our purpose is to identify the pathogenic variations associated with BDA-1 involved in a five-generation Chinese family. METHODS: A BDA-1 family with 8 affected and 14 unaffected family members was recruited. Whole exome sequencing (WES) was performed to identify the pathogenic variant in the proband, and which was later confirmed and segregated by Sanger sequencing. The significance of variants were assessed using several molecular and bioinformatics analysis methods. RESULTS: We uncovered a novel heterozygous missense variant c.299A > G (p.D100G) at the mutational hotspot of IHH gene following whole-exome sequencing of a Chinese family with BDA-1. The variant co-segregated with BDA-1 in the pedigree, showed 100% penetrance for phalange phenotype with variable expressivity. CONCLUSIONS: In conclusion, this study reports a five-generation Chinese family with BDA-1 due to a novel pathogenic variant (c.299A > G (p.D100G)) of IHH and expands the clinical and genetic spectrum of BDA-1.
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spelling pubmed-70925352020-03-24 A novel variant of IHH in a Chinese family with brachydactyly type 1 Yang, Qi Wang, Jin Tian, Xiaoxian Shen, Fei Lan, Jing Zhang, Qiang Fan, Xin Yi, Shang Li, Mengting Shen, Yiping BMC Med Genet Research Article BACKGROUND: Brachydactyly type A1(BDA-1) is an autosomal dominant disorder which is caused by heterozygous pathogenic variants in a specific region of the N-terminal active fragment of Indian Hedgehog (IHH). The disorder is mainly characterized by shortening or missing of the middle phalanges. In this study, Our purpose is to identify the pathogenic variations associated with BDA-1 involved in a five-generation Chinese family. METHODS: A BDA-1 family with 8 affected and 14 unaffected family members was recruited. Whole exome sequencing (WES) was performed to identify the pathogenic variant in the proband, and which was later confirmed and segregated by Sanger sequencing. The significance of variants were assessed using several molecular and bioinformatics analysis methods. RESULTS: We uncovered a novel heterozygous missense variant c.299A > G (p.D100G) at the mutational hotspot of IHH gene following whole-exome sequencing of a Chinese family with BDA-1. The variant co-segregated with BDA-1 in the pedigree, showed 100% penetrance for phalange phenotype with variable expressivity. CONCLUSIONS: In conclusion, this study reports a five-generation Chinese family with BDA-1 due to a novel pathogenic variant (c.299A > G (p.D100G)) of IHH and expands the clinical and genetic spectrum of BDA-1. BioMed Central 2020-03-24 /pmc/articles/PMC7092535/ /pubmed/32209048 http://dx.doi.org/10.1186/s12881-020-01000-6 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Yang, Qi
Wang, Jin
Tian, Xiaoxian
Shen, Fei
Lan, Jing
Zhang, Qiang
Fan, Xin
Yi, Shang
Li, Mengting
Shen, Yiping
A novel variant of IHH in a Chinese family with brachydactyly type 1
title A novel variant of IHH in a Chinese family with brachydactyly type 1
title_full A novel variant of IHH in a Chinese family with brachydactyly type 1
title_fullStr A novel variant of IHH in a Chinese family with brachydactyly type 1
title_full_unstemmed A novel variant of IHH in a Chinese family with brachydactyly type 1
title_short A novel variant of IHH in a Chinese family with brachydactyly type 1
title_sort novel variant of ihh in a chinese family with brachydactyly type 1
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7092535/
https://www.ncbi.nlm.nih.gov/pubmed/32209048
http://dx.doi.org/10.1186/s12881-020-01000-6
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