A p.Arg499His mutation in SPAST is associated with infantile-onset complicated spastic paraplegia: a case report and review of the literature

Abstract Background Spastic paraplegia type 4 (SPG4) is caused by mutations in the SPAST gene, is the most common form of autosomal-dominant pure hereditary spastic paraplegias (HSP), and is rarely associated with a complicated form that includes ataxia, epilepsy, and cognitive decline. To date, the...

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Autores principales:	Haitian Nan, Hiroshi Shiraku, Tomoko Mizuno, Yoshihisa Takiyama
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Hereditary spastic paraplegia SPG4 Complicated form P.Arg499His Case report Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/2de1a4e4804d4d0097855afef05aabf7
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spelling	oai:doaj.org-article:2de1a4e4804d4d0097855afef05aabf72021-11-14T12:13:29ZA p.Arg499His mutation in SPAST is associated with infantile-onset complicated spastic paraplegia: a case report and review of the literature10.1186/s12883-021-02478-01471-2377https://doaj.org/article/2de1a4e4804d4d0097855afef05aabf72021-11-01T00:00:00Zhttps://doi.org/10.1186/s12883-021-02478-0https://doaj.org/toc/1471-2377Abstract Background Spastic paraplegia type 4 (SPG4) is caused by mutations in the SPAST gene, is the most common form of autosomal-dominant pure hereditary spastic paraplegias (HSP), and is rarely associated with a complicated form that includes ataxia, epilepsy, and cognitive decline. To date, the genotype-phenotype correlation has not been substantially established for SPAST mutations. Case presentation We present a Japanese patient with infantile-onset HSP and a complex form with coexisting ataxia and epilepsy. The sequencing of SPAST revealed a de novo c.1496G > A (p.R499H) mutation. A review of the literature revealed 16 additional patients with p.R499H mutations in SPAST associated with an early-onset complicated form of HSP. We found that the complicated phenotype of patients with p.Arg499His mutations could be mainly divided into three subgroups: (1) infantile-onset ascending hereditary spastic paralysis, (2) HSP with severe dystonia, and (3) HSP with cognitive impairment. Moreover, the c.1496G > A mutation in SPAST may occur as a de novo variant at noticeably high rates. Conclusion We reviewed the clinical features of the patients reported in the literature with the p.Arg499His mutation in SPAST and described the case of a Japanese patient with this mutation presenting a new complicated form. Accumulating evidence suggests a possible association between infantile-onset complicated HSP and the p.Arg499His mutation in SPAST. The findings of this study may expand the clinical spectrum of the p.Arg499His mutation in SPAST and provide an opportunity to further study the genotype-phenotype correlation of SPG4.Haitian NanHiroshi ShirakuTomoko MizunoYoshihisa TakiyamaBMCarticleHereditary spastic paraplegiaSPG4Complicated formP.Arg499HisCase reportNeurology. Diseases of the nervous systemRC346-429ENBMC Neurology, Vol 21, Iss 1, Pp 1-5 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Hereditary spastic paraplegia SPG4 Complicated form P.Arg499His Case report Neurology. Diseases of the nervous system RC346-429
spellingShingle	Hereditary spastic paraplegia SPG4 Complicated form P.Arg499His Case report Neurology. Diseases of the nervous system RC346-429 Haitian Nan Hiroshi Shiraku Tomoko Mizuno Yoshihisa Takiyama A p.Arg499His mutation in SPAST is associated with infantile-onset complicated spastic paraplegia: a case report and review of the literature
description	Abstract Background Spastic paraplegia type 4 (SPG4) is caused by mutations in the SPAST gene, is the most common form of autosomal-dominant pure hereditary spastic paraplegias (HSP), and is rarely associated with a complicated form that includes ataxia, epilepsy, and cognitive decline. To date, the genotype-phenotype correlation has not been substantially established for SPAST mutations. Case presentation We present a Japanese patient with infantile-onset HSP and a complex form with coexisting ataxia and epilepsy. The sequencing of SPAST revealed a de novo c.1496G > A (p.R499H) mutation. A review of the literature revealed 16 additional patients with p.R499H mutations in SPAST associated with an early-onset complicated form of HSP. We found that the complicated phenotype of patients with p.Arg499His mutations could be mainly divided into three subgroups: (1) infantile-onset ascending hereditary spastic paralysis, (2) HSP with severe dystonia, and (3) HSP with cognitive impairment. Moreover, the c.1496G > A mutation in SPAST may occur as a de novo variant at noticeably high rates. Conclusion We reviewed the clinical features of the patients reported in the literature with the p.Arg499His mutation in SPAST and described the case of a Japanese patient with this mutation presenting a new complicated form. Accumulating evidence suggests a possible association between infantile-onset complicated HSP and the p.Arg499His mutation in SPAST. The findings of this study may expand the clinical spectrum of the p.Arg499His mutation in SPAST and provide an opportunity to further study the genotype-phenotype correlation of SPG4.
format	article
author	Haitian Nan Hiroshi Shiraku Tomoko Mizuno Yoshihisa Takiyama
author_facet	Haitian Nan Hiroshi Shiraku Tomoko Mizuno Yoshihisa Takiyama
author_sort	Haitian Nan
title	A p.Arg499His mutation in SPAST is associated with infantile-onset complicated spastic paraplegia: a case report and review of the literature
title_short	A p.Arg499His mutation in SPAST is associated with infantile-onset complicated spastic paraplegia: a case report and review of the literature
title_full	A p.Arg499His mutation in SPAST is associated with infantile-onset complicated spastic paraplegia: a case report and review of the literature
title_fullStr	A p.Arg499His mutation in SPAST is associated with infantile-onset complicated spastic paraplegia: a case report and review of the literature
title_full_unstemmed	A p.Arg499His mutation in SPAST is associated with infantile-onset complicated spastic paraplegia: a case report and review of the literature
title_sort	p.arg499his mutation in spast is associated with infantile-onset complicated spastic paraplegia: a case report and review of the literature
publisher	BMC
publishDate	2021
url	https://doaj.org/article/2de1a4e4804d4d0097855afef05aabf7
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A p.Arg499His mutation in SPAST is associated with infantile-onset complicated spastic paraplegia: a case report and review of the literature

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