Two novel truncating variants in UBAP1 are responsible for hereditary spastic paraplegia.

Hereditary spastic paraplegias (HSPs) are a group of rare neurodegenerative disorders. HSPs are complex disorders and are clinically and genetically heterogeneous. To date, more than 80 genes or genetic loci have been reported to be responsible for HSPs in a Mendelian-dependent manner. Most recently...

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Autores principales:	Xinchao Bian, Guangying Cheng, Xinbo Sun, Hongkun Liu, Xiangmao Zhang, Yu Han, Bo Li, Ning Li
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a4de2833c7a248f08fe64f3e6a132506
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spelling	oai:doaj.org-article:a4de2833c7a248f08fe64f3e6a1325062021-12-02T20:15:42ZTwo novel truncating variants in UBAP1 are responsible for hereditary spastic paraplegia.1932-620310.1371/journal.pone.0253871https://doaj.org/article/a4de2833c7a248f08fe64f3e6a1325062021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0253871https://doaj.org/toc/1932-6203Hereditary spastic paraplegias (HSPs) are a group of rare neurodegenerative disorders. HSPs are complex disorders and are clinically and genetically heterogeneous. To date, more than 80 genes or genetic loci have been reported to be responsible for HSPs in a Mendelian-dependent manner. Most recently, ubiquitin-associated protein 1 (UBAP1) has been recognized to be involved in HSP. Here, we identified novel protein truncating variants in two families with pure form of HSP. A novel deletion (c.468_469delTG) in the UBAP1 gene was found in the first family, whereas a nonsense variant (c.512T>G) was ascertained in the second family. The variants were confirmed in all patients but were not detected in unaffected family members. The mutations resulted in truncated proteins of UBAP1. The variants did not result in different subcellular localizations in neuro-2a cells. However, each of the two variants impaired neurite outgrowth. Taken together, our findings expand the pathogenic spectrum of UBAP1 variants in HSP.Xinchao BianGuangying ChengXinbo SunHongkun LiuXiangmao ZhangYu HanBo LiNing LiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 6, p e0253871 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xinchao Bian Guangying Cheng Xinbo Sun Hongkun Liu Xiangmao Zhang Yu Han Bo Li Ning Li Two novel truncating variants in UBAP1 are responsible for hereditary spastic paraplegia.
description	Hereditary spastic paraplegias (HSPs) are a group of rare neurodegenerative disorders. HSPs are complex disorders and are clinically and genetically heterogeneous. To date, more than 80 genes or genetic loci have been reported to be responsible for HSPs in a Mendelian-dependent manner. Most recently, ubiquitin-associated protein 1 (UBAP1) has been recognized to be involved in HSP. Here, we identified novel protein truncating variants in two families with pure form of HSP. A novel deletion (c.468_469delTG) in the UBAP1 gene was found in the first family, whereas a nonsense variant (c.512T>G) was ascertained in the second family. The variants were confirmed in all patients but were not detected in unaffected family members. The mutations resulted in truncated proteins of UBAP1. The variants did not result in different subcellular localizations in neuro-2a cells. However, each of the two variants impaired neurite outgrowth. Taken together, our findings expand the pathogenic spectrum of UBAP1 variants in HSP.
format	article
author	Xinchao Bian Guangying Cheng Xinbo Sun Hongkun Liu Xiangmao Zhang Yu Han Bo Li Ning Li
author_facet	Xinchao Bian Guangying Cheng Xinbo Sun Hongkun Liu Xiangmao Zhang Yu Han Bo Li Ning Li
author_sort	Xinchao Bian
title	Two novel truncating variants in UBAP1 are responsible for hereditary spastic paraplegia.
title_short	Two novel truncating variants in UBAP1 are responsible for hereditary spastic paraplegia.
title_full	Two novel truncating variants in UBAP1 are responsible for hereditary spastic paraplegia.
title_fullStr	Two novel truncating variants in UBAP1 are responsible for hereditary spastic paraplegia.
title_full_unstemmed	Two novel truncating variants in UBAP1 are responsible for hereditary spastic paraplegia.
title_sort	two novel truncating variants in ubap1 are responsible for hereditary spastic paraplegia.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/a4de2833c7a248f08fe64f3e6a132506
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Two novel truncating variants in UBAP1 are responsible for hereditary spastic paraplegia.

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