Evidence for pathogenicity of variant ATM Val1729Leu in a family with ataxia telangiectasia
Tóm tắt
Ataxia telangiectasia is a rare autosomal recessive multisystem disorder caused by mutations in the gene of ATM serine/threonine kinase. It is characterized by neurodegeneration, leading to severe ataxia, immunodeficiency, increased cancer susceptibility, and telangiectasia. Here, we discovered a co-segregation of two ATM gene variants with ataxia telangiectasia in an Egyptian family. While one of these variants (NM_000051.4(ATM_i001):p.(Val128*)) has previously been reported as pathogenic, the other one (NM_000051.4(ATM_i001):p.(Val1729Leu)) is regarded as a variant of uncertain significance. Our findings in this family provide additional evidence for causality of the second variant and argue that its status should be changed to pathogenic.
Tài liệu tham khảo
Levy A, Lang AE (2018) Ataxia-telangiectasia: a review of movement disorders, clinical features, and genotype correlations. Mov Disord 33(8):1238–1247. https://doi.org/10.1002/mds.27319
Rothblum-Oviatt C, Wright J, Lefton-Greif MA, McGrath-Morrow SA, Crawford TO, Lederman HM (2016) Ataxia telangiectasia: a review. Orphanet J Rare Dis 11(1):159. https://doi.org/10.1186/s13023-016-0543-7
Savitsky K, Bar-Shira A, Gilad S, Rotman G, Ziv Y, Vanagaite L, Tagle DA, Smith S, Uziel T, Sfez S, Ashkenazi M, Pecker I, Frydman M, Harnik R, Patanjali SR, Simmons A, Clines GA, Sartiel A, Gatti RA, Chessa L, Sanal O, Lavin MF, Jaspers NG, Taylor AM, Arlett CF, Miki T, Weissman SM, Lovett M, Collins FS, Shiloh Y (1995) A single ataxia telangiectasia gene with a product similar to PI-3 kinase. Science. 268(5218):1749–1753. https://doi.org/10.1126/science.7792600
Chang X, Wang K (2012) wANNOVAR: annotating genetic variants for personal genomes via the web. J Med Genet 49(7):433–436. https://doi.org/10.1136/jmedgenet-2012-100918
Kircher M, Witten DM, Jain P, O'Roak BJ, Cooper GM, Shendure J (2014) A general framework for estimating the relative pathogenicity of human genetic variants. Nat Genet 46(3):310–315. https://doi.org/10.1038/ng.2892
Schwarz JM, Cooper DN, Schuelke M, Seelow D (2014) MutationTaster2: mutation prediction for the deep-sequencing age. Nat Methods 11(4):361–362. https://doi.org/10.1038/nmeth.2890
Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, Kondrashov AS, Sunyaev SR (2010) A method and server for predicting damaging missense mutations. Nat Methods 7(4):248–249. https://doi.org/10.1038/nmeth0410-248
Stenson PD, Mort M, Ball EV, Chapman M, Evans K, Azevedo L, Hayden M, Heywood S, Millar DS, Phillips AD, Cooper DN (2020) The Human Gene Mutation Database (HGMD((R))): optimizing its use in a clinical diagnostic or research setting. Hum Genet 139(10):1197–1207. https://doi.org/10.1007/s00439-020-02199-3
Landrum MJ, Lee JM, Benson M, Brown GR, Chao C, Chitipiralla S, Gu B, Hart J, Hoffman D, Jang W, Karapetyan K, Katz K, Liu C, Maddipatla Z, Malheiro A, McDaniel K, Ovetsky M, Riley G, Zhou G, Holmes JB, Kattman BL, Maglott DR (2018) ClinVar: improving access to variant interpretations and supporting evidence. Nucleic Acids Res 46(D1):D1062–D10D7. https://doi.org/10.1093/nar/gkx1153
Fokkema IF, Taschner PE, Schaafsma GC, Celli J, Laros JF, den Dunnen JT (2011) LOVD v.2.0: the next generation in gene variant databases. Hum Mutat 32(5):557–563. https://doi.org/10.1002/humu.21438
Podralska MJ, Stembalska A, Ślęzak R, Lewandowicz-Uszyńska A, Pietrucha B, Kołtan S, Wigowska-Sowińska J, Pilch J, Mosor M, Ziółkowska-Suchanek I, Dzikiewicz-Krawczyk A, Słomski R (2014) Ten new ATM alterations in Polish patients with ataxia-telangiectasia. Mol Genet Genomic Med 2(6):504–511. https://doi.org/10.1002/mgg3.98
Mitui M, Bernatowska E, Pietrucha B, Piotrowska-Jastrzebska J, Eng L, Nahas S, Teraoka S, Sholty G, Purayidom A, Concannon P, Gatti RA (2005) ATM gene founder haplotypes and associated mutations in Polish families with ataxia-telangiectasia. Ann Hum Genet 69(Pt 6):657–664. https://doi.org/10.1111/j.1529-8817.2005.00199.x
Magliozzi M, Piane M, Torrente I, Sinibaldi L, Rizzo G, Savio C, Lulli P, de Luca A, Dallapiccola B, Chessa L (2006) DHPLC screening of ATM gene in Italian patients affected by ataxia-telangiectasia: fourteen novel ATM mutations. Dis Markers 22(4):257–264. https://doi.org/10.1155/2006/740493
George Priya Doss C, Rajith B (2012) Computational refinement of functional single nucleotide polymorphisms associated with ATM gene. PLoS One 7(4):e34573. https://doi.org/10.1371/journal.pone.0034573
Coutelier M, Hammer MB, Stevanin G, Monin ML, Davoine CS, Mochel F, Labauge P, Ewenczyk C, Ding J, Gibbs JR, Hannequin D, Melki J, Toutain A, Laugel V, Forlani S, Charles P, Broussolle E, Thobois S, Afenjar A, Anheim M, Calvas P, Castelnovo G, de Broucker T, Vidailhet M, Moulignier A, Ghnassia RT, Tallaksen C, Mignot C, Goizet C, le Ber I, Ollagnon-Roman E, Pouget J, Brice A, Singleton A, Durr A, for the Spastic Paraplegia and Ataxia Network (2018) Efficacy of exome-targeted capture sequencing to detect mutations in known cerebellar ataxia genes. JAMA Neurol 75(5):591–599. https://doi.org/10.1001/jamaneurol.2017.5121
Paucar M, Taylor AMR, Hadjivassiliou M, Fogel BL, Svenningsson P (2019) Progressive ataxia with elevated alpha-fetoprotein: diagnostic issues and review of the literature. Tremor Other Hyperkinet Mov (NY) 9. https://doi.org/10.7916/tohm.v0.708