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山东大学学报 (医学版) ›› 2019, Vol. 57 ›› Issue (11): 78-82.doi: 10.6040/j.issn.1671-7554.0.2019.482

• • 上一篇    

SYNE1基因复合杂合突变导致常染色体隐性小脑共济失调1型病例报告并文献复习

胡丽萍1,王乐2,金亮1,刘燕霞1,崔东清1,曹丽丽1   

  1. 1.山东大学齐鲁医院神经内科, 山东 济南 250012;2. 德州市人民医院神经内科, 山东 德州 253056
  • 发布日期:2022-09-27
  • 通讯作者: 曹丽丽. E-mail:qilucll@163.com
  • 基金资助:
    山东省自然科学基金(ZR2016HM68)

A case report and literature review of complex heterozygous SYNE1 mutation with autosomal recessive cerebellar ataxia type1

HU Liping1, WANG Le2, JIN Liang1, LIU Yanxia1, CUI Dongqing1, CAO Lili1   

  1. 1. Department of Neurology, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China;
    2. Department of Neurology, Peoples Hospital of Dezhou, Dezhou 253056, Shandong, China
  • Published:2022-09-27

摘要: 目的 对一个常染色体隐性小脑共济失调1型(ARCA1)家系进行基因测序,以寻找该家系的致病基因。 方法 对1例慢性进行性小脑性共济失调的青年女性患者进行临床检验和神经影像学检查,并进行基因目标区域捕获和高通量测序。 结果 靶区捕获测序发现,在SYNE1基因的67号外显子的10 887位点(c. 10887dupT)和41号外显子的5 995位点( c.5995A>T,p.K1999 X )存在复合杂合突变。桑格测序的结果也在患者的父母中得到了确认。 结论 在SYNE1中发现了两个新的复合杂合突变,这是我国首次报道的具有SYNE1基因突变的ARCA1患者。

关键词: 常染色体隐性小脑共济失调1型, SYNE1基因突变, 高通量测序, 共济失调

Abstract: Objective To search for the disease-causing gene in a family with autosomal recessive cerebellar ataxia type 1(ARCA1). Methods The young female with chronic progressive ARCA received clinical examination, neuroimaging, target region capture and high-throughput sequencing. Results Target region capture sequencing yielded compound heterozygous mutations in exon 67 at codon 10 887(c.10887dupT)and exon 41 at codon 5 995(c.5995A>2T, p. K1999X)of the SYNE1 gene. The results of Sanger sequencing were identified in the patients parents. Conclusion Two novel compound heterozygous mutations in SYNE1 are identified and an ARCA1 family with novel SYNE1 gene mutation is reported for the first time in China.

Key words: Autosomal recessive cerebellar ataxia type 1, SYNE1 gene mutations, High-throughput sequencing, Ataxia

中图分类号: 

  • R744.7
[1] Gros-Louis F, Dupré N, Dion P, et al. Mutations in SYNE1 lead to a newly discovered form of autosomal recessive cerebellar ataxia[J]. Nat Genet, 2007,39(1): 80-85.
[2] Noreau A, Bourassa CV, Szuto A, et al. SYNE1 mutations in autosomal recessive cerebellar ataxia[J]. JAMA Neurol, 2013, 70(10): 1296-1301.
[3] Yoshinaga T, Nakamura K, ishikawa M, et al. A novel frameshift mutation of SYNE1 in a Japanese family with autosomal recessive cerebellar ataxia type 8[J]. Hum Genome Var, 2017, 4: 17052. doi: 10.1038/hgv.2017.52.
[4] Hamza W, Ali Pacha L, Hamadouche T, et al. Molecular and clinical study of a cohort of 110 Algerian patients with autosomal recessive ataxia[J]. BMC Med Genet, 2015,16: 36. doi 10.1186/s12881-015-0180-3.
[5] Gama MT, Houle G, Noreau A, et al. SYNE1 mutations cause autosomal-recessive ataxia with retained reflexes in Brazilian patients[J]. Mov Disord, 2016, 31(11): 1754-1756.
[6] Algahtani H, Marzouk Y, Algahtani R, et al. Autosomal recessive ataxia type 1 mimicking multiple sclerosis: a report of two siblings with a novel mutation in SYNE1 gene in a Saudi family[J]. J Neurol Sci, 2017, 372(1): 97-100.
[7] Yucesan E, Ugur Iseri SA, Bilgic B, et al. SYNE1 related cerebellar ataxia presents with variable phenotypes in a consanguineous family from Turkey[J]. Neurol Sci, 2017, 38(12): 2203-2207.
[8] Lzumi Y, Miyamoto R, Morino H, et al. Cerebellar ataxia with SYNE1 mutation accompanying motor neuron disease[J]. Neurology, 2013, 80(6): 600-601.
[9] Synofzik M, mets K, Mallaret M, et al. SYNE1 ataxia is a common recessive ataxia with major non-cerebellar features: a large scale multi-centre study[J]. Brain, 2016, 139(5): 1378-1393.
[10] Wiethoff S, Hersheson J, Bettencourt C, et al. Heterogeneity in clinical features and disease severity in ataxia-associated SYNE1 mutations[J]. J Neurol, 2016, 263(8): 1503-1510.
[11] Laforce R Jr, Buteau JP, Bouchard JP, et al. Cognitive impairment in ARCA-1, a newly discovered pure cerebellar ataxia syndrome[J]. Cerebellum, 2010, 9(3): 443-453.
[12] Swan L, Cardinal J, Coman D. SYNE1-related autosomal recessive cerebellar ataxia, congenital cerebellar hypoplasia, and cognitive impairment[J]. Clin Pract, 2018, 8(3): 1071. doi: 10.4081/cp.2018.1071.
[13] Thiffault I, Dicaire MJ, Tetreault M, et al. Diversity of ARSACS mutations in French-Canadians[J]. Can J Neurol Sci, 2013, 40(1): 61-66.
[14] Duquette A, Roddier K, McNabb-Baltar J, et al. Mutations in senataxin responsible for Quebec cluster of ataxia with neuropathy[J]. Ann Neurol, 2005, 57(3): 408-414.
[15] Dupre N, Gros-louis F, Chrestian N, et al. Clinical and genetic study of autosomal recessive cerebellar ataxia type 1[J]. Ann Neurol, 2007, 62(1): 93-98.
[16] Puckelwartz MJ, Kessler E, Zhang Y, et al. Disruption of nesprin-1 produces an Emery Dreifuss muscular dystrophy- like phenotype in mice[J]. Hum Mol Genet, 2009, 18(4): 607-620.
[17] Zhang J, Felder A, Liu Y, et al. Nesprin 1 is critical for nuclear positioning and anchorage[J]. Hum Mol Genet, 2010, 19(2): 329-341. doi: 10.1093/hmg/ddp499.
[18] Attali R, Warwar N, Israel A, et al. Mutation of SYNE-1, encoding an essential component of the nuclear lamina, is responsible for autosomal recessive arthrogryposis[J]. Hum Mol Genet, 2009, 18(18): 3462-3469.
[19] Chen Z, Ren Z, Mei W, et al. A novel SYNE1 gene mutation in a Chinese family of Emery-Dreifuss muscular dystrophy-like[J]. BMC Medical Genetics, 2017, 18(1): 63. doi: 10.1186/s12881-017-0424-5.
[20] Zhang Q, Bethmann C, Worth NF, et al. Nesprin-1 and -2 are involved in the pathogenesis of Emery-Dreifuss muscular dystrophy and are critical for nuclear envelope integrity[J]. Hum Mol Genet, 2007, 16(23): 2816-2833.
[21] Fanin M, Savarese M, Nascimbeni AC, et al. Dominant muscular dystrophy with a novel SYNE1 gene mutation[J]. Muscle Nerve, 2015, 51(1): 145-147.
[22] Ikeda Y, Dick KA, Weatherspoon MR, et al. Spectrin mutations cause spinocerebellar ataxia type 5[J]. Nat Genet, 2006, 38(2): 184-190.
[23] Ishikawa K, Toru S, Tsunemi T, et al. An autosomal dominant cerebellar ataxia linked to chromosome 16q22.1 is associated with a single-nucleotide subtitution in the 5; untranslated region of the gene encoding a protein with spectrin repeat and Rho guanine-nucleotide exchange-factor domains[J]. Am J Hum Genet, 2005, 77(2): 280-296.
[24] Stevanin G, Herman A, Brice A, et al. Clinical and MRI findings in Spinocerebellar ataxia type 5[J]. Neurology, 1999, 53(6): 1355-1357.
[25] Burk K, Zuhlke C, Konig IR, et al. Spinocerebellar ataxia type 5: clinical and molecular genetic features of a German kindred[J]. Neurology, 2004, 62(2): 327-329.
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