Detection of TSC1/TSC2 mosaic variants in patients with cardiac rhabdomyoma and tuberous sclerosis complex by hybrid‐capture next‐generation sequencing

Abstract Background Fetal cardiac rhabdomyoma (CR) is strongly associated with tuberous sclerosis complex (TSC), which is caused by variants in TSC1 and TSC2. However, in 10%–15% of patients with clinically confirmed TSC, no TSC1/TSC2 variants are identified by panel sequencing or multiplex ligation...

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Autores principales:	Siyu Wang, Hairui Sun, Jianbin Wang, Xiaoyan Gu, Lu Han, Yuduo Wu, He Yan, Ling Han, Hongjia Zhang, Yihua He
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	cardiac rhabdomyoma hybrid‐capture next‐generation sequencing mosaic variants TSC1/TSC2 Genetics QH426-470
Acceso en línea:	https://doaj.org/article/67b6eb58aff24834afd012b639c90274
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spelling	oai:doaj.org-article:67b6eb58aff24834afd012b639c902742021-11-10T16:39:24ZDetection of TSC1/TSC2 mosaic variants in patients with cardiac rhabdomyoma and tuberous sclerosis complex by hybrid‐capture next‐generation sequencing2324-926910.1002/mgg3.1802https://doaj.org/article/67b6eb58aff24834afd012b639c902742021-10-01T00:00:00Zhttps://doi.org/10.1002/mgg3.1802https://doaj.org/toc/2324-9269Abstract Background Fetal cardiac rhabdomyoma (CR) is strongly associated with tuberous sclerosis complex (TSC), which is caused by variants in TSC1 and TSC2. However, in 10%–15% of patients with clinically confirmed TSC, no TSC1/TSC2 variants are identified by panel sequencing or multiplex ligation‐dependent probe amplification (MLPA). Methods We analyzed eight fetuses with CR and their families. No TSC1/TSC2 variants had previously been identified for six of these fetuses, and we suspected the other two families of gonadal mosaicism. We performed next‐generation sequencing (NGS) using CR tissue, umbilical cord tissue, and parental blood. All positive results, involving two paternal semen, were verified by droplet digital polymerase chain reaction (ddPCR). Results Four fetuses carried low‐level mosaic variants (0.05%–14.89%), and two only exhibited somatic mosaic variants in the CR tissue (15.76% and 37.69%). Two fathers had gonadal mosaicism (9.07% and 4.86%). We identified nine pathogenic variants in eight fetuses, including one fetus with a second‐hit variant. Conclusion The fetuses assessed in this study carried low‐level and somatic mosaic variants, and CR tissue from one fetus exhibited a second‐hit variant. Heterozygous gonadal variants can exist in patients with low‐level mosaicism. Combining NGS with ddPCR improves the accuracy of prenatal TSC diagnosis.Siyu WangHairui SunJianbin WangXiaoyan GuLu HanYuduo WuHe YanLing HanHongjia ZhangYihua HeWileyarticlecardiac rhabdomyomahybrid‐capture next‐generation sequencingmosaic variantsTSC1/TSC2GeneticsQH426-470ENMolecular Genetics & Genomic Medicine, Vol 9, Iss 10, Pp n/a-n/a (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cardiac rhabdomyoma hybrid‐capture next‐generation sequencing mosaic variants TSC1/TSC2 Genetics QH426-470
spellingShingle	cardiac rhabdomyoma hybrid‐capture next‐generation sequencing mosaic variants TSC1/TSC2 Genetics QH426-470 Siyu Wang Hairui Sun Jianbin Wang Xiaoyan Gu Lu Han Yuduo Wu He Yan Ling Han Hongjia Zhang Yihua He Detection of TSC1/TSC2 mosaic variants in patients with cardiac rhabdomyoma and tuberous sclerosis complex by hybrid‐capture next‐generation sequencing
description	Abstract Background Fetal cardiac rhabdomyoma (CR) is strongly associated with tuberous sclerosis complex (TSC), which is caused by variants in TSC1 and TSC2. However, in 10%–15% of patients with clinically confirmed TSC, no TSC1/TSC2 variants are identified by panel sequencing or multiplex ligation‐dependent probe amplification (MLPA). Methods We analyzed eight fetuses with CR and their families. No TSC1/TSC2 variants had previously been identified for six of these fetuses, and we suspected the other two families of gonadal mosaicism. We performed next‐generation sequencing (NGS) using CR tissue, umbilical cord tissue, and parental blood. All positive results, involving two paternal semen, were verified by droplet digital polymerase chain reaction (ddPCR). Results Four fetuses carried low‐level mosaic variants (0.05%–14.89%), and two only exhibited somatic mosaic variants in the CR tissue (15.76% and 37.69%). Two fathers had gonadal mosaicism (9.07% and 4.86%). We identified nine pathogenic variants in eight fetuses, including one fetus with a second‐hit variant. Conclusion The fetuses assessed in this study carried low‐level and somatic mosaic variants, and CR tissue from one fetus exhibited a second‐hit variant. Heterozygous gonadal variants can exist in patients with low‐level mosaicism. Combining NGS with ddPCR improves the accuracy of prenatal TSC diagnosis.
format	article
author	Siyu Wang Hairui Sun Jianbin Wang Xiaoyan Gu Lu Han Yuduo Wu He Yan Ling Han Hongjia Zhang Yihua He
author_facet	Siyu Wang Hairui Sun Jianbin Wang Xiaoyan Gu Lu Han Yuduo Wu He Yan Ling Han Hongjia Zhang Yihua He
author_sort	Siyu Wang
title	Detection of TSC1/TSC2 mosaic variants in patients with cardiac rhabdomyoma and tuberous sclerosis complex by hybrid‐capture next‐generation sequencing
title_short	Detection of TSC1/TSC2 mosaic variants in patients with cardiac rhabdomyoma and tuberous sclerosis complex by hybrid‐capture next‐generation sequencing
title_full	Detection of TSC1/TSC2 mosaic variants in patients with cardiac rhabdomyoma and tuberous sclerosis complex by hybrid‐capture next‐generation sequencing
title_fullStr	Detection of TSC1/TSC2 mosaic variants in patients with cardiac rhabdomyoma and tuberous sclerosis complex by hybrid‐capture next‐generation sequencing
title_full_unstemmed	Detection of TSC1/TSC2 mosaic variants in patients with cardiac rhabdomyoma and tuberous sclerosis complex by hybrid‐capture next‐generation sequencing
title_sort	detection of tsc1/tsc2 mosaic variants in patients with cardiac rhabdomyoma and tuberous sclerosis complex by hybrid‐capture next‐generation sequencing
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/67b6eb58aff24834afd012b639c90274
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Detection of TSC1/TSC2 mosaic variants in patients with cardiac rhabdomyoma and tuberous sclerosis complex by hybrid‐capture next‐generation sequencing

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