Identification of a novel COL10A1: c.1952 G>T variant in a family with Schmid metaphyseal chondrodysplasia and development of a noninvasive prenatal testing method

Abstract Background The collagen alpha‐1(X) chain gene (COL10A1) is a known causative gene for Schmid metaphyseal chondrodysplasia (SMCD). This study clinically examined a Chinese family (n = 42) for SMCD and inheritance pattern. Fifteen individuals were diagnosed with SMCD based on characteristic s...

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Autores principales:	Yanchou Ye, Weihao Li, Guan Wang, Longsheng Zhan, Junwei Lin, Tian Li, Jun Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	COL10A1 noninvasive prenatal testing pathogenic variant Sanger sequencing Schmid metaphyseal chondrodysplasia (SMCD) trio‐whole exome sequencing Genetics QH426-470
Acceso en línea:	https://doaj.org/article/f3382b9a793d4a758843d73a1c83f42b
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spelling	oai:doaj.org-article:f3382b9a793d4a758843d73a1c83f42b2021-11-10T16:39:23ZIdentification of a novel COL10A1: c.1952 G>T variant in a family with Schmid metaphyseal chondrodysplasia and development of a noninvasive prenatal testing method2324-926910.1002/mgg3.1758https://doaj.org/article/f3382b9a793d4a758843d73a1c83f42b2021-10-01T00:00:00Zhttps://doi.org/10.1002/mgg3.1758https://doaj.org/toc/2324-9269Abstract Background The collagen alpha‐1(X) chain gene (COL10A1) is a known causative gene for Schmid metaphyseal chondrodysplasia (SMCD). This study clinically examined a Chinese family (n = 42) for SMCD and inheritance pattern. Fifteen individuals were diagnosed with SMCD based on characteristic skeletal phenotypes with autosomal dominant inheritance mode. Methods Four clinically diagnosed patients and three healthy relatives were selected for subsequent genetic tests. Trio‐whole exome sequencing (Trio‐WES) followed by Sanger sequencing and familial co‐segregation analysis were performed to identify SMCD‐associated variants. Results COL10A1 (NM_000493.4):c.1952 G>T(p.Trp651Leu) variant was detected only in the four patients and not in the three healthy relatives. The variant was evaluated as “likely pathogenic” according to the American College of Medical Genetics and Genomics variation classification guidelines with evidence of PM2, PM5, PP1, and PP3. To test the presence of the target variant in proband's fetal offspring, we developed a noninvasive prenatal testing method by extracting cell‐free fetal DNA in maternal plasma followed by high‐depth sequencing. The variant was also detected in the fetus and later confirmed by amniocentesis. Conclusion We identified a new disease‐causing variant in COL10A1. Cell‐free fetal DNA in maternal peripheral blood can be used as the rapid and noninvasive prenatal diagnostic method to detect the pathogenic/or likely pathogenic variant.Yanchou YeWeihao LiGuan WangLongsheng ZhanJunwei LinTian LiJun ZhangWileyarticleCOL10A1noninvasive prenatal testingpathogenic variantSanger sequencingSchmid metaphyseal chondrodysplasia (SMCD)trio‐whole exome sequencingGeneticsQH426-470ENMolecular Genetics & Genomic Medicine, Vol 9, Iss 10, Pp n/a-n/a (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	COL10A1 noninvasive prenatal testing pathogenic variant Sanger sequencing Schmid metaphyseal chondrodysplasia (SMCD) trio‐whole exome sequencing Genetics QH426-470
spellingShingle	COL10A1 noninvasive prenatal testing pathogenic variant Sanger sequencing Schmid metaphyseal chondrodysplasia (SMCD) trio‐whole exome sequencing Genetics QH426-470 Yanchou Ye Weihao Li Guan Wang Longsheng Zhan Junwei Lin Tian Li Jun Zhang Identification of a novel COL10A1: c.1952 G>T variant in a family with Schmid metaphyseal chondrodysplasia and development of a noninvasive prenatal testing method
description	Abstract Background The collagen alpha‐1(X) chain gene (COL10A1) is a known causative gene for Schmid metaphyseal chondrodysplasia (SMCD). This study clinically examined a Chinese family (n = 42) for SMCD and inheritance pattern. Fifteen individuals were diagnosed with SMCD based on characteristic skeletal phenotypes with autosomal dominant inheritance mode. Methods Four clinically diagnosed patients and three healthy relatives were selected for subsequent genetic tests. Trio‐whole exome sequencing (Trio‐WES) followed by Sanger sequencing and familial co‐segregation analysis were performed to identify SMCD‐associated variants. Results COL10A1 (NM_000493.4):c.1952 G>T(p.Trp651Leu) variant was detected only in the four patients and not in the three healthy relatives. The variant was evaluated as “likely pathogenic” according to the American College of Medical Genetics and Genomics variation classification guidelines with evidence of PM2, PM5, PP1, and PP3. To test the presence of the target variant in proband's fetal offspring, we developed a noninvasive prenatal testing method by extracting cell‐free fetal DNA in maternal plasma followed by high‐depth sequencing. The variant was also detected in the fetus and later confirmed by amniocentesis. Conclusion We identified a new disease‐causing variant in COL10A1. Cell‐free fetal DNA in maternal peripheral blood can be used as the rapid and noninvasive prenatal diagnostic method to detect the pathogenic/or likely pathogenic variant.
format	article
author	Yanchou Ye Weihao Li Guan Wang Longsheng Zhan Junwei Lin Tian Li Jun Zhang
author_facet	Yanchou Ye Weihao Li Guan Wang Longsheng Zhan Junwei Lin Tian Li Jun Zhang
author_sort	Yanchou Ye
title	Identification of a novel COL10A1: c.1952 G>T variant in a family with Schmid metaphyseal chondrodysplasia and development of a noninvasive prenatal testing method
title_short	Identification of a novel COL10A1: c.1952 G>T variant in a family with Schmid metaphyseal chondrodysplasia and development of a noninvasive prenatal testing method
title_full	Identification of a novel COL10A1: c.1952 G>T variant in a family with Schmid metaphyseal chondrodysplasia and development of a noninvasive prenatal testing method
title_fullStr	Identification of a novel COL10A1: c.1952 G>T variant in a family with Schmid metaphyseal chondrodysplasia and development of a noninvasive prenatal testing method
title_full_unstemmed	Identification of a novel COL10A1: c.1952 G>T variant in a family with Schmid metaphyseal chondrodysplasia and development of a noninvasive prenatal testing method
title_sort	identification of a novel col10a1: c.1952 g>t variant in a family with schmid metaphyseal chondrodysplasia and development of a noninvasive prenatal testing method
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/f3382b9a793d4a758843d73a1c83f42b
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Identification of a novel COL10A1: c.1952 G>T variant in a family with Schmid metaphyseal chondrodysplasia and development of a noninvasive prenatal testing method

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