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19.03.2024 | Original Article

Whole exome sequencing in Serbian patients with hereditary spastic paraplegia

verfasst von: Marija Brankovic, Vukan Ivanovic, Ivana Basta, Rin Khang, Eugene Lee, Zorica Stevic, Branislav Ralic, Radoje Tubic, GoHun Seo, Vladana Markovic, Ivo Bozovic, Marina Svetel, Ana Marjanovic, Nikola Veselinovic, Sarlota Mesaros, Milena Jankovic, Dusanka Savic-Pavicevic, Zita Jovin, Ivana Novakovic, Hane Lee, Stojan Peric

Erschienen in: Neurogenetics

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Abstract

Hereditary spastic paraplegia (HSP) is a group of neurodegenerative diseases with a high genetic and clinical heterogeneity. Numerous HSP patients remain genetically undiagnosed despite screening for known genetic causes of HSP. Therefore, identification of novel variants and genes is needed. Our previous study analyzed 74 adult Serbian HSP patients from 65 families using panel of the 13 most common HSP genes in combination with a copy number variation analysis. Conclusive genetic findings were established in 23 patients from 19 families (29%). In the present study, nine patients from nine families previously negative on the HSP gene panel were selected for the whole exome sequencing (WES). Further, 44 newly diagnosed adult HSP patients from 44 families were sent to WES directly, since many studies showed WES may be used as the first step in HSP diagnosis. WES analysis of cohort 1 revealed a likely genetic cause in five (56%) of nine HSP families, including variants in the ETHE1, ZFYVE26, RNF170, CAPN1, and WASHC5 genes. In cohort 2, possible causative variants were found in seven (16%) of 44 patients (later updated to 27% when other diagnosis were excluded), comprising six different genes: SPAST, SPG11, WASCH5, KIF1A, KIF5A, and ABCD1. These results expand the genetic spectrum of HSP patients in Serbia and the region with implications for molecular genetic diagnosis and future causative therapies. Wide HSP panel can be the first step in diagnosis, alongside with the copy number variation (CNV) analysis, while WES should be performed after.

de Souza PVS, de Rezende Pinto WBV, de Rezende Batistella GN, Bortholin T, Oliveira ASB (2017) Hereditary Spastic Paraplegia: Clinical and Genetic Hallmarks. Cerebellum 16(2):525–551PubMedCrossRef

Ruano L, Melo C, Silva MC, Coutinho P (2014) The global epidemiology of hereditary ataxia and spastic paraplegia: a systematic review of prevalence studies. Neuroepidemiology 42(3):174–183PubMedCrossRef

Schüle R, Wiethoff S, Martus P et al (2016) Hereditary spastic paraplegia: Clinicogenetic lessons from 608 patients. Ann Neurol 79(4):646–658PubMedCrossRef

Murala S, Nagarajan E, Bollu PC (2021) Hereditary spastic paraplegia. Neurol Sci 42(3):883–894PubMedCrossRef

Darios F, Coarelli G, Durr A (2022) Genetics in hereditary spastic paraplegias: Essential but not enough. Curr Opin Neurobiol 72:8–14PubMedCrossRef

Meyyazhagan A, Kuchi Bhotla H, Pappuswamy M, Orlacchio A (2022) The Puzzle of Hereditary Spastic Paraplegia: From Epidemiology to Treatment. Int J Mol Sci 23(14):7665 (Published 2022 Jul 11)PubMedPubMedCentralCrossRef

Iqbal Z, Rydning SL, Wedding IM et al (2017) Correction: Targeted high throughput sequencing in hereditary ataxia and spastic paraplegia. PLoS One 12(10):e0186571 (Published 2017 Oct 12)PubMedPubMedCentralCrossRef

Méreaux JL, Banneau G, Papin M et al (2022) Clinical and genetic spectra of 1550 index patients with hereditary spastic paraplegia. Brain 145(3):1029–1037PubMedCrossRef

Perić S, Marković V, Candayan A et al (2022) Phenotypic and Genetic Heterogeneity of Adult Patients with Hereditary Spastic Paraplegia from Serbia. Cells 11(18):2804 (Published 2022 Sep 8)PubMedPubMedCentralCrossRef

10.

Hedera P (2000) Hereditary Spastic Paraplegia Overview. In: Adam MP, Feldman J, Mirzaa GM et al (eds) GeneReviews®. University of Washington, Seattle, Seattle (WA)

11.

Seo GH, Kim T, Choi IH et al (2020) Diagnostic yield and clinical utility of whole exome sequencing using an automated variant prioritization system, EVIDENCE. Clin Genet 98(6):562–570PubMedPubMedCentralCrossRef

12.

Karczewski KJ, Francioli LC, Tiao G et al (2020) The mutational constraint spectrum quantified from variation in 141,456 humans. Nature. 581(7809):434–443 ([published correction appears in Nature. 2021 Feb;590(7846):E53] [published correction appears in Nature. 2021 Sep;597(7874):E3-E4])ADSPubMedPubMedCentralCrossRef

13.

Richards S, Aziz N, Bale S et al (2015) Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 17(5):405–424PubMedPubMedCentralCrossRef

14.

Köhler S, Gargano M, Matentzoglu N et al (2021) The Human Phenotype Ontology in 2021. Nucleic Acids Res 49(D1):D1207–D1217PubMedCrossRef

15.

Köhler S, Schulz MH, Krawitz P et al (2009) Clinical diagnostics in human genetics with semantic similarity searches in ontologies. Am J Hum Genet 85(4):457–464PubMedPubMedCentralCrossRef

16.

Greene D, BioResource NIHR, Richardson S, Turro E (2016) Phenotype Similarity Regression for Identifying the Genetic Determinants of Rare Diseases. Am J Hum Genet 98(3):490–499. https://doi.org/10.1016/j.ajhg.2016.01.008CrossRefPubMedPubMedCentral

17.

D’Amore A, Tessa A, Casali C et al (2018) Next Generation Molecular Diagnosis of Hereditary Spastic Paraplegias: An Italian Cross-Sectional Study. Front Neurol 9:981 (Published 2018 Dec 4)PubMedPubMedCentralCrossRef

18.

Cui F, Sun L, Qiao J et al (2020) Genetic mutation analysis of hereditary spastic paraplegia: A retrospective study. Medicine (Baltimore) 99(23):e20193PubMedCrossRef

19.

Valencia CA, Husami A, Holle J et al (2015) Clinical Impact and Cost-Effectiveness of Whole Exome Sequencing as a Diagnostic Tool: A Pediatric Center’s Experience. Front Pediatr 3:67 (Published 2015 Aug 3)PubMedPubMedCentralCrossRef

20.

Zhao M, Chen YJ, Wang MW et al (2019) Genetic and Clinical Profile of Chinese Patients with Autosomal Dominant Spastic Paraplegia. Mol Diagn Ther 23(6):781–789PubMedCrossRef

21.

Schiavoni S, Spagnoli C, Rizzi S et al (2020) Paediatric-onset hereditary spastic paraplegias: a retrospective cohort study. Dev Med Child Neurol 62(9):1068–1074PubMedCrossRef

22.

Mandelker D, Schmidt RJ, Ankala A et al (2016) Navigating highly homologous genes in a molecular diagnostic setting: a resource for clinical next-generation sequencing. Genet Med 18(12):1282–1289PubMedCrossRef

23.

Cummings BB, Marshall JL, Tukiainen T et al (2017) Improving genetic diagnosis in Mendelian disease with transcriptome sequencing. Sci Transl Med 9(386):eaal5209PubMedPubMedCentralCrossRef

24.

Kremer LS, Bader DM, Mertes C et al (2017) Genetic diagnosis of Mendelian disorders via RNA sequencing. Nat Commun 8:15824ADSPubMedPubMedCentralCrossRef

25.

Frésard L, Smail C, Ferraro NM et al (2019) Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts. Nat Med 25(6):911–919PubMedPubMedCentralCrossRef

26.

Lee H, Huang AY, Wang LK et al (2020) Diagnostic utility of transcriptome sequencing for rare Mendelian diseases. Genet Med 22(3):490–499PubMedCrossRef

27.

Logsdon GA, Vollger MR, Eichler EE (2020) Long-read human genome sequencing and its applications. Nat Rev Genet 21(10):597–614PubMedPubMedCentralCrossRef

28.

Yang JO, Yoon JY, Sung DH et al (2021) The emerging genetic diversity of hereditary spastic paraplegia in Korean patients. Genomics 113(6):4136–4148PubMedCrossRef

29.

Fussiger H, Pereira BLDS, Padilha JPD et al (2023) Copy number variations in SPAST and ATL1 are rare among Brazilians. Clin Genet 103(5):580–584PubMedCrossRef

30.

Drousiotou A, DiMeo I, Mineri R, Georgiou T, Stylianidou G, Tiranti V (2011) Ethylmalonic encephalopathy: application of improved biochemical and molecular diagnostic approaches. Clin Genet 79(4):385–390PubMedCrossRef

31.

Kitzler TM, Gupta IR, Osterman B et al (2019) Acute and Chronic Management in an Atypical Case of Ethylmalonic Encephalopathy. JIMD Rep 45:57–63PubMedCrossRef

32.

Pigeon N, Campeau PM, Cyr D, Lemieux B, Clarke JT (2009) Clinical heterogeneity in ethylmalonic encephalopathy. J Child Neurol 24(8):991–996PubMedCrossRef

33.

Müller vom Hagen J, Karle KN, Schüle R, Krägeloh-Mann I, Schöls L (2014) Leukodystrophies underlying cryptic spastic paraparesis: frequency and phenotype in 76 patients. Eur J Neurol 21(7):983–988PubMedCrossRef

34.

Hershkovitz E, Narkis G, Shorer Z et al (2002) Cerebral X-linked adrenoleukodystrophy in a girl with Xq27-Ter deletion. Ann Neurol 52(2):234–237PubMedCrossRef

35.

Jung HH, Wimplinger I, Jung S, Landau K, Gal A, Heppner FL (2007) Phenotypes of female adrenoleukodystrophy. Neurology 68(12):960–961PubMedCrossRef

36.

Moser HW (1997) Adrenoleukodystrophy: phenotype, genetics, pathogenesis and therapy. Brain 120(Pt 8):1485–1508PubMedCrossRef

37.

Engelen M, van Ballegoij WJC, Mallack EJ et al (2022) International Recommendations for the Diagnosis and Management of Patients With Adrenoleukodystrophy: A Consensus-Based Approach. Neurology 99(21):940–951PubMedPubMedCentralCrossRef

38.

Olgiati S, Doğu O, Tufekcioglu Z et al (2017) The p.Thr11Met mutation in c19orf12 is frequent among adult Turkish patients with MPAN. Parkinsonism Relat Disord. 39:64–70PubMedCrossRef

39.

Fraser S, Koenig M, Farach L, Mancias P, Mowrey K (2021) A De Novo case of autosomal dominant mitochondrial membrane protein-associated neurodegeneration. Mol Genet Genomic Med 9(7):e1706PubMedPubMedCentralCrossRef

40.

Rickman OJ, Salter CG, Gunning AC et al (2021) Dominant mitochondrial membrane protein-associated neurodegeneration (MPAN) variants cluster within a specific C19orf12 isoform. Parkinsonism Relat Disord 82:84–86PubMedCrossRef

41.

Hartig MB, Iuso A, Haack T et al (2011) Absence of an orphan mitochondrial protein, c19orf12, causes a distinct clinical subtype of neurodegeneration with brain iron accumulation. Am J Hum Genet 89(4):543–550PubMedPubMedCentralCrossRef

42.

Hogarth P, Gregory A, Kruer MC et al (2013) New NBIA subtype: genetic, clinical, pathologic, and radiographic features of MPAN. Neurology 80(3):268–275PubMedPubMedCentralCrossRef

43.

Schulte EC, Claussen MC, Jochim A et al (2013) Mitochondrial membrane protein associated neurodegenration: a novel variant of neurodegeneration with brain iron accumulation. Mov Disord 28(2):224–227PubMedCrossRef

44.

Selikhova M, Fedotova E, Wiethoff S et al (2017) A 30-year history of MPAN case from Russia. Clin Neurol Neurosurg 159:111–113PubMedCrossRef

45.

Sparber P, Marakhonov A, Filatova A, Sharkova I, Skoblov M (2018) Novel case of neurodegeneration with brain iron accumulation 4 (NBIA4) caused by a pathogenic variant affecting splicing. Neurogenetics 19(4):257–260PubMedCrossRef

46.

Gregory A, Lotia M, Jeong SY et al (2019) Autosomal dominant mitochondrial membrane protein-associated neurodegeneration (MPAN). Mol Genet Genomic Med 7(7):e00736PubMedPubMedCentralCrossRef

47.

Gregory A, Klopstock T, Kmiec T, Hogarth P, Hayflick SJ (2014) Mitochondrial Membrane Protein-Associated Neurodegeneration. In: Adam MP, Feldman J, Mirzaa GM et al (eds) GeneReviews®. University of Washington, Seattle, Seattle (WA)

48.

Sparber P, Krylova T, Repina S et al (2021) Retrospective analysis of 17 patients with mitochondrial membrane protein-associated neurodegeneration diagnosed in Russia. Parkinsonism Relat Disord 84:98–104PubMedCrossRef

49.

Dursun U, Koroglu C, Kocasoy Orhan E, Ugur SA, Tolun A (2009) Autosomal recessive spastic paraplegia (SPG45) with mental retardation maps to 10q24.3–q25.1. Neurogenetics 10(4):325–331PubMedCrossRef

50.

Novarino G, Fenstermaker AG, Zaki MS et al (2014) Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders. Science 343(6170):506–511ADSPubMedPubMedCentralCrossRef

51.

Elsaid MF, Ibrahim K, Chalhoub N, Elsotouhy A, El Mudehki N, Abdel Aleem A (2017) NT5C2 novel splicing variant expands the phenotypic spectrum of Spastic Paraplegia (SPG45): case report of a new member of thin corpus callosum SPG-Subgroup. BMC Med Genet 18(1):33 (Published 2017 Mar 21)PubMedPubMedCentralCrossRef

52.

Shenoy VS, Sampath R (2023) Syringomyelia. In: statpearls. Treasure island (FL): statpearls publishing. https://www.ncbi.nlm.nih.gov/books/NBK537110/. Accessed 10 Apr 2023

53.

Arnoldi A, Crimella C, Tenderini E et al (2012) Clinical phenotype variability in patients with hereditary spastic paraplegia type 5 associated with CYP7B1 mutations. Clin Genet 81(2):150–157PubMedCrossRef

54.

Theuriet J, Pegat A, Leblanc P et al (2021) Phenoconversion from Spastic Paraplegia to ALS/FTD Associated with CYP7B1 Compound Heterozygous Mutations. Genes (Basel) 12(12):1876 (Published 2021 Nov 25)PubMedCrossRef

55.

Goizet C, Boukhris A, Durr A et al (2009) CYP7B1 mutations in pure and complex forms of hereditary spastic paraplegia type 5. Brain 132(Pt 6):1589–1600PubMedCrossRef

56.

Schlipf NA, Schüle R, Klimpe S et al (2011) Amplicon-based high-throughput pooled sequencing identifies mutations in CYP7B1 and SPG7 in sporadic spastic paraplegia patients. Clin Genet 80(2):148–160PubMedCrossRef

57.

Kumar KR, Blair NF, Vandebona H et al (2013) Targeted next generation sequencing in SPAST-negative hereditary spastic paraplegia. J Neurol 260(10):2516–2522PubMedCrossRef

58.

Roos P, Svenstrup K, Danielsen ER, Thomsen C, Nielsen JE (2014) CYP7B1: novel mutations and magnetic resonance spectroscopy abnormalities in hereditary spastic paraplegia type 5A. Acta Neurol Scand 129(5):330–334PubMedCrossRef

59.

Goizet C, Boukhris A, Maltete D et al (2009) SPG15 is the second most common cause of hereditary spastic paraplegia with thin corpus callosum. Neurology 73(14):1111–1119PubMedCrossRef

Titel: Whole exome sequencing in Serbian patients with hereditary spastic paraplegia
verfasst von: Marija Brankovic
Vukan Ivanovic
Ivana Basta
Rin Khang
Eugene Lee
Zorica Stevic
Branislav Ralic
Radoje Tubic
GoHun Seo
Vladana Markovic
Ivo Bozovic
Marina Svetel
Ana Marjanovic
Nikola Veselinovic
Sarlota Mesaros
Milena Jankovic
Dusanka Savic-Pavicevic
Zita Jovin
Ivana Novakovic
Hane Lee
Stojan Peric
Publikationsdatum: 19.03.2024
Verlag: Springer Berlin Heidelberg
Erschienen in: Neurogenetics
Print ISSN: 1364-6745
Elektronische ISSN: 1364-6753
DOI: https://doi.org/10.1007/s10048-024-00755-x

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