Identification of de novo mutations for ARID1B haploinsufficiency associated with Coffin–Siris syndrome 1 in three Chinese families via array-CGH and whole exome sequencing

Abstract Background Coffin–Siris syndrome (CSS) is a multiple malformation syndrome characterized by intellectual disability associated with coarse facial features, hirsutism, sparse scalp hair, and hypoplastic or absent fifth fingernails or toenails. CSS represents a small group of intellectual dis...

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Autores principales:	Guanting Lu, Qiongling Peng, Lianying Wu, Jian Zhang, Liya Ma
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Haploinsufficiency ARID1B Coffin–Siris syndrome SWI/SNF complex Microdeletion Loss-of-function Internal medicine RC31-1245 Genetics QH426-470
Acceso en línea:	https://doaj.org/article/8fc446d3d2d541438e35afb0700a2402
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spelling	oai:doaj.org-article:8fc446d3d2d541438e35afb0700a24022021-11-21T12:04:20ZIdentification of de novo mutations for ARID1B haploinsufficiency associated with Coffin–Siris syndrome 1 in three Chinese families via array-CGH and whole exome sequencing10.1186/s12920-021-01119-21755-8794https://doaj.org/article/8fc446d3d2d541438e35afb0700a24022021-11-01T00:00:00Zhttps://doi.org/10.1186/s12920-021-01119-2https://doaj.org/toc/1755-8794Abstract Background Coffin–Siris syndrome (CSS) is a multiple malformation syndrome characterized by intellectual disability associated with coarse facial features, hirsutism, sparse scalp hair, and hypoplastic or absent fifth fingernails or toenails. CSS represents a small group of intellectual disability, and could be caused by at least twelve genes. The genetic background is quite heterogenous, making it difficult for clinicians and genetic consultors to pinpoint the exact disease types. Methods Array-Comparative Genomic Hybridization (array-CGH) and whole exome sequencing (WES) were applied for three trios affected with intellectual disability and clinical features similar with those of Coffin–Siris syndrome. Sanger sequencing was used to verify the detected single-nucleotide variants (SNVs). Results All of the three cases were female with normal karyotypes of 46, XX, born of healthy, non-consanguineous parents. A 6q25 microdeletion (arr[hg19]6q25.3(155,966,487–158,803,979) × 1) (2.84 Mb) (case 1) and two loss-of-function (LoF) mutations of ARID1B [c.2332 + 1G > A in case 2 and c.4741C > T (p.Q1581X) in case 3] were identified. All of the three pathogenic abnormalities were de novo, not inherited from their parents. After comparison of publicly available microdeletions containing ARID1B, four types of microdeletions leading to insufficient production of ARID1B were identified, namely deletions covering the whole region of ARID1B, deletions covering the promoter region, deletions covering the termination region or deletions covering enhancer regions. Conclusion Here we identified de novo ARID1B mutations in three Chinese trios. Four types of microdeletions covering ARID1B were identified. This study broadens current knowledge of ARID1B mutations for clinicians and genetic consultors.Guanting LuQiongling PengLianying WuJian ZhangLiya MaBMCarticleHaploinsufficiencyARID1BCoffin–Siris syndromeSWI/SNF complexMicrodeletionLoss-of-functionInternal medicineRC31-1245GeneticsQH426-470ENBMC Medical Genomics, Vol 14, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Haploinsufficiency ARID1B Coffin–Siris syndrome SWI/SNF complex Microdeletion Loss-of-function Internal medicine RC31-1245 Genetics QH426-470
spellingShingle	Haploinsufficiency ARID1B Coffin–Siris syndrome SWI/SNF complex Microdeletion Loss-of-function Internal medicine RC31-1245 Genetics QH426-470 Guanting Lu Qiongling Peng Lianying Wu Jian Zhang Liya Ma Identification of de novo mutations for ARID1B haploinsufficiency associated with Coffin–Siris syndrome 1 in three Chinese families via array-CGH and whole exome sequencing
description	Abstract Background Coffin–Siris syndrome (CSS) is a multiple malformation syndrome characterized by intellectual disability associated with coarse facial features, hirsutism, sparse scalp hair, and hypoplastic or absent fifth fingernails or toenails. CSS represents a small group of intellectual disability, and could be caused by at least twelve genes. The genetic background is quite heterogenous, making it difficult for clinicians and genetic consultors to pinpoint the exact disease types. Methods Array-Comparative Genomic Hybridization (array-CGH) and whole exome sequencing (WES) were applied for three trios affected with intellectual disability and clinical features similar with those of Coffin–Siris syndrome. Sanger sequencing was used to verify the detected single-nucleotide variants (SNVs). Results All of the three cases were female with normal karyotypes of 46, XX, born of healthy, non-consanguineous parents. A 6q25 microdeletion (arr[hg19]6q25.3(155,966,487–158,803,979) × 1) (2.84 Mb) (case 1) and two loss-of-function (LoF) mutations of ARID1B [c.2332 + 1G > A in case 2 and c.4741C > T (p.Q1581X) in case 3] were identified. All of the three pathogenic abnormalities were de novo, not inherited from their parents. After comparison of publicly available microdeletions containing ARID1B, four types of microdeletions leading to insufficient production of ARID1B were identified, namely deletions covering the whole region of ARID1B, deletions covering the promoter region, deletions covering the termination region or deletions covering enhancer regions. Conclusion Here we identified de novo ARID1B mutations in three Chinese trios. Four types of microdeletions covering ARID1B were identified. This study broadens current knowledge of ARID1B mutations for clinicians and genetic consultors.
format	article
author	Guanting Lu Qiongling Peng Lianying Wu Jian Zhang Liya Ma
author_facet	Guanting Lu Qiongling Peng Lianying Wu Jian Zhang Liya Ma
author_sort	Guanting Lu
title	Identification of de novo mutations for ARID1B haploinsufficiency associated with Coffin–Siris syndrome 1 in three Chinese families via array-CGH and whole exome sequencing
title_short	Identification of de novo mutations for ARID1B haploinsufficiency associated with Coffin–Siris syndrome 1 in three Chinese families via array-CGH and whole exome sequencing
title_full	Identification of de novo mutations for ARID1B haploinsufficiency associated with Coffin–Siris syndrome 1 in three Chinese families via array-CGH and whole exome sequencing
title_fullStr	Identification of de novo mutations for ARID1B haploinsufficiency associated with Coffin–Siris syndrome 1 in three Chinese families via array-CGH and whole exome sequencing
title_full_unstemmed	Identification of de novo mutations for ARID1B haploinsufficiency associated with Coffin–Siris syndrome 1 in three Chinese families via array-CGH and whole exome sequencing
title_sort	identification of de novo mutations for arid1b haploinsufficiency associated with coffin–siris syndrome 1 in three chinese families via array-cgh and whole exome sequencing
publisher	BMC
publishDate	2021
url	https://doaj.org/article/8fc446d3d2d541438e35afb0700a2402
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Identification of de novo mutations for ARID1B haploinsufficiency associated with Coffin–Siris syndrome 1 in three Chinese families via array-CGH and whole exome sequencing

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