四个法国家族中 SPAST 变异携带者的嵌合体证据。
Evidence of mosaicism in SPAST variant carriers in four French families.
机构信息
Service de Génétique Médicale, CHU Bordeaux, Bordeaux, Bordeaux, France.
Centre de Référence Maladies Rares Neurogénétique, Service de Génétique Médicale, Bordeaux, France.
出版信息
Eur J Hum Genet. 2021 Jul;29(7):1158-1163. doi: 10.1038/s41431-021-00847-4. Epub 2021 May 6.
Abstract
Hereditary spastic paraplegias (HSP) are heterogeneous disorders, with more than 70 causative genes. Variants in SPAST are the most frequent genetic etiology and are responsible for spastic paraplegia type 4 (SPG4). Age at onset can vary, even between patients from the same family, and incomplete penetrance is described. Somatic mosaicism is extremely rare with only three patients reported in the literature. We report here SPAST mosaic variants in four unrelated patients. We confirm that mosaicism in SPAST is a very rare event with only four identified cases on more than 300 patients with a SPAST variant previously described by our clinical diagnostic laboratory.
摘要
遗传性痉挛性截瘫（HSP）是一种异质性疾病，有 70 多个致病基因。SPAST 中的变异是最常见的遗传病因，导致痉挛性截瘫 4 型（SPG4）。发病年龄可有所不同，即使是同一家庭的患者之间也是如此，并且存在不完全外显率的情况。体细胞嵌合极为罕见，文献中仅报道了 3 例患者。我们在此报告 4 例无关联患者的 SPAST 嵌合变异。我们证实，SPAST 嵌合是一种非常罕见的事件，在我们临床诊断实验室之前描述的 300 多例 SPAST 变异患者中，仅发现了 4 例。
相似文献
1
Evidence of mosaicism in SPAST variant carriers in four French families.四个法国家族中 SPAST 变异携带者的嵌合体证据。
Eur J Hum Genet. 2021 Jul;29(7):1158-1163. doi: 10.1038/s41431-021-00847-4. Epub 2021 May 6.
2
A novel SPAST gene mutation identified in a Chinese family with hereditary spastic paraplegia.在中国一个遗传性痉挛性截瘫家族中鉴定出一种新的痉挛蛋白（SPAST）基因突变。
BMC Med Genet. 2020 Jun 3;21(1):123. doi: 10.1186/s12881-020-01053-7.
3
A complex form of hereditary spastic paraplegia in three siblings due to somatic mosaicism for a novel SPAST mutation in the mother.由于母亲存在一种新的SPAST突变的体细胞镶嵌现象，三名兄弟姐妹患有复杂形式的遗传性痉挛性截瘫。
J Neurol Sci. 2014 Dec 15;347(1-2):352-5. doi: 10.1016/j.jns.2014.09.046. Epub 2014 Oct 2.
4
A Japanese SPG4 Patient with a Confirmed De Novo Mutation of the SPAST Gene.一位日本 SPG4 患者，携带 SPAST 基因的新生突变。
Intern Med. 2020 Sep 15;59(18):2311-2315. doi: 10.2169/internalmedicine.4599-20. Epub 2020 Jun 9.
5
[Hereditary spastic paraplegia type 4 (SPG4) in Russian patients].[俄罗斯患者的遗传性痉挛性截瘫4型（SPG4）]
Zh Nevrol Psikhiatr Im S S Korsakova. 2019;119(11):11-20. doi: 10.17116/jnevro201911911111.
6
Novel and recurrent spastin mutations in a large series of SPG4 Italian families.在一大系列 SPG4 意大利家族中发现新型和复发性的 spastin 突变。
Neurosci Lett. 2012 Oct 18;528(1):42-5. doi: 10.1016/j.neulet.2012.08.036. Epub 2012 Aug 25.
7
The investigation of genetic and clinical features in patients with hereditary spastic paraplegia in central-Southern China.中国中南部遗传性痉挛性截瘫患者的遗传和临床特征研究。
Mol Genet Genomic Med. 2021 May;9(5):e1627. doi: 10.1002/mgg3.1627. Epub 2021 Feb 27.
8
Spastin accumulation and motor neuron defects caused by a novel SPAST splice site mutation.一种新型 SPAST 剪接位点突变导致的痉挛蛋白积累和运动神经元缺陷。
J Transl Med. 2024 Sep 27;22(1):872. doi: 10.1186/s12967-024-05669-8.
9
Spastic paraplegia due to SPAST mutations is modified by the underlying mutation and sex.由 SPAST 突变引起的痉挛性截瘫受潜在突变和性别的影响。
Brain. 2018 Dec 1;141(12):3331-3342. doi: 10.1093/brain/awy285.
10
A novel variant (p.A524P) in Spastin is responsible for a Chinese family with hereditary spastic paraplegia.一个新的 Spastin 变异（p.A524P）导致了一个中国遗传性痉挛性截瘫家系。
Mol Biol Rep. 2024 Sep 4;51(1):951. doi: 10.1007/s11033-024-09880-0.
引用本文的文献
1
A novel variant of in a pedigree with pure hereditary spastic paraplegia in Yunnan Province.云南省一个患有纯遗传性痉挛性截瘫家系中的一种新型变异。
Ann Transl Med. 2022 Jan;10(2):67. doi: 10.21037/atm-21-6698.
2
Insights into Clinical, Genetic, and Pathological Aspects of Hereditary Spastic Paraplegias: A Comprehensive Overview.遗传性痉挛性截瘫的临床、遗传和病理方面的见解：全面概述
Front Mol Biosci. 2021 Nov 26;8:690899. doi: 10.3389/fmolb.2021.690899. eCollection 2021.
3
Clinical genetics-it's polygenic.临床遗传学——它是多基因的。
Eur J Hum Genet. 2021 Jul;29(7):1037. doi: 10.1038/s41431-021-00931-9.
本文引用的文献
1
A p.Arg499His Mutation in SPAST Is Associated with Infantile Onset Ascending Spastic Paralysis Complicated with Dysarthria and Anarthria.痉挛蛋白（SPAST）中的p.Arg499His突变与婴儿期起病的上行性痉挛性麻痹合并构音障碍和完全性失语相关。
Neuropediatrics. 2019 Dec;50(6):391-394. doi: 10.1055/s-0039-1694973. Epub 2019 Sep 4.
2
De novo SPAST mutations may cause a complex SPG4 phenotype.新生SPAST突变可能导致复杂的SPG4表型。
Brain. 2019 Jul 1;142(7):e31. doi: 10.1093/brain/awz140.
3
Spastic paraplegia due to SPAST mutations is modified by the underlying mutation and sex.由 SPAST 突变引起的痉挛性截瘫受潜在突变和性别的影响。
Brain. 2018 Dec 1;141(12):3331-3342. doi: 10.1093/brain/awy285.
4
Massive sequencing of 70 genes reveals a myriad of missing genes or mechanisms to be uncovered in hereditary spastic paraplegias.对70个基因进行大规模测序揭示了遗传性痉挛性截瘫中大量有待发现的缺失基因或机制。
Eur J Hum Genet. 2017 Nov;25(11):1217-1228. doi: 10.1038/ejhg.2017.124. Epub 2017 Aug 23.
5
A de novo mosaic mutation in SPAST with two novel alternative alleles and chromosomal copy number variant in a boy with spastic paraplegia and autism spectrum disorder.一名患有痉挛性截瘫和自闭症谱系障碍的男孩中，SPAST基因存在一个具有两个新的替代等位基因的从头镶嵌突变以及染色体拷贝数变异。
Eur J Med Genet. 2017 Oct;60(10):548-552. doi: 10.1016/j.ejmg.2017.07.015. Epub 2017 Aug 1.
6
MME mutation in dominant spinocerebellar ataxia with neuropathy (SCA43).MME 突变导致显性遗传性脊髓小脑共济失调伴周围神经病（SCA43）。
Neurol Genet. 2016 Aug 18;2(5):e94. doi: 10.1212/NXG.0000000000000094. eCollection 2016 Oct.
7
A series of Greek children with pure hereditary spastic paraplegia: clinical features and genetic findings.一系列患有单纯遗传性痉挛性截瘫的希腊儿童：临床特征与基因研究结果
J Neurol. 2016 Aug;263(8):1604-11. doi: 10.1007/s00415-016-8179-z. Epub 2016 Jun 3.
8
Mutations in MME cause an autosomal-recessive Charcot-Marie-Tooth disease type 2.MME基因的突变会导致常染色体隐性2型夏科-马里-图思病。
Ann Neurol. 2016 Apr;79(4):659-72. doi: 10.1002/ana.24612. Epub 2016 Mar 17.
9
Mutational spectrum of the SPAST and ATL1 genes in Korean patients with hereditary spastic paraplegia.韩国遗传性痉挛性截瘫患者中SPAST和ATL1基因的突变谱。
J Neurol Sci. 2015 Oct 15;357(1-2):167-72. doi: 10.1016/j.jns.2015.07.024. Epub 2015 Jul 17.
10
Hereditary spastic paraplegia SPG4: what is known and not known about the disease.遗传性痉挛性截瘫SPG4：关于该疾病已知和未知的情况
Brain. 2015 Sep;138(Pt 9):2471-84. doi: 10.1093/brain/awv178. Epub 2015 Jun 20.
Zotero 插件