Journal of Neurology

, Volume 259, Issue 5, pp 906–911 | Cite as

ANO10 c.1150_1151del is a founder mutation causing autosomal recessive cerebellar ataxia in Roma/Gypsies

  • Teodora Chamova
  • Laura Florez
  • Velina Guergueltcheva
  • Margarita Raycheva
  • Radka Kaneva
  • Hanns Lochmüller
  • Luba Kalaydjieva
  • Ivailo Tournev
Original Communication

Abstract

A recent report (Vermeer et al. in Am J Hum Genet 87:813–819, 2010) implicated for the first time the ANO10 gene in the genetic basis of autosomal recessive cerebellar ataxias. One of the three described families were Roma/Gypsies from Serbia, where the affected individuals were homozygous for the truncating p.Leu384fs mutation and displayed distinct phenotypic features (Vermeer et al. in Am J Hum Genet 87:813–819, 2010). Based on the history and population genetics of the Roma/Gypsies, we hypothesised that p.Leu384fs could be another founder mutation in this population, whose identification in a larger number of genetically homogeneous patients will contribute to defining the phenotypic spectrum of the disorder. Here, we describe additional patients from neighbouring Bulgaria, outlining invariable ANO10-ataxia features and confirming global intellectual decline as part of the phenotype resulting from complete Anactomin 10 deficit.

Keywords

Autosomal recessive cerebellar ataxia ANO10 Phenotypic features Gypsy founder mutations 

Supplementary material

415_2011_6276_MOESM1_ESM.docx (13 kb)
Supplementary material 1 (DOCX 13 kb)

References

  1. 1.
    Vermeer S, Hoischen A, Meijer RP, Gilissen C, Neveling K, Wieskamp N, de Brouwer A, Koenig M, Anheim M, Assoum M, Drouot N, Todorovic S, Milic-Rasic V, Lochmuller H, Stevanin G, Goizet C, David A, Durr A, Brice A, Kremer B, van de Warrenburg BP, Schijvenaars MM, Heister A, Kwint M, Arts P, van der Wijst J, Veltman J, Kamsteeg EJ, Scheffer H, Knoers N (2010) Targeted next-generation sequencing of a 12.5 Mb homozygous region reveals ANO10 mutations in patients with autosomal-recessive cerebellar ataxia. Am J Hum Genet 87(6):813–819. doi:10.1016/j.ajhg.2010.10.015 (S0002-9297(10)00531-8 [pii])PubMedCrossRefGoogle Scholar
  2. 2.
    Harding AE (1983) Classification of the hereditary ataxias and paraplegias. Lancet 1(8334):1151–1155 (S0140-6736(83)92879-9 [pii])PubMedCrossRefGoogle Scholar
  3. 3.
    Finsterer J (2009) Ataxias with autosomal, X-chromosomal or maternal inheritance. Can J Neurol Sci 36(4):409–428PubMedGoogle Scholar
  4. 4.
    H’Mida-Ben Brahim D, M’Zahem A, Assoum M, Bouhlal Y, Fattori F, Anheim M, Ali-Pacha L, Ferrat F, Chaouch M, Lagier-Tourenne C, Drouot N, Thibaut C, Benhassine T, Sifi Y, Stoppa-Lyonnet D, N’Guyen K, Poujet J, Hamri A, Hentati F, Amouri R, Santorelli FM, Tazir M, Koenig M (2011) Molecular diagnosis of known recessive ataxias by homozygosity mapping with SNP arrays. J Neurol 258(1):56–67. doi:10.1007/s00415-010-5682-5 PubMedCrossRefGoogle Scholar
  5. 5.
    Kalaydjieva L, Morar B, Chaix R, Tang H (2005) A newly discovered founder population: the Roma/Gypsies. Bioessays 27(10):1084–1094. doi:10.1002/bies.20287 PubMedCrossRefGoogle Scholar
  6. 6.
    Mihaylova V, Hantke J, Sinigerska I, Cherninkova S, Raicheva M, Bouwer S, Tincheva R, Khuyomdziev D, Bertranpetit J, Chandler D, Angelicheva D, Kremensky I, Seeman P, Tournev I, Kalaydjieva L (2007) Highly variable neural involvement in sphingomyelinase-deficient Niemann-Pick disease caused by an ancestral Gypsy mutation. Brain 130(Pt 4):1050–1061. doi:10.1093/brain/awm026 (awm026 [pii])PubMedGoogle Scholar
  7. 7.
    Gresham D, Morar B, Underhill PA, Passarino G, Lin AA, Wise C, Angelicheva D, Calafell F, Oefner PJ, Shen P, Tournev I, de Pablo R, Kucinskas V, Perez-Lezaun A, Marushiakova E, Popov V, Kalaydjieva L (2001) Origins and divergence of the Roma (gypsies). Am J Hum Genet 69(6):1314–1331. doi:10.1086/324681 (S0002-9297(07)61261-0 [pii])PubMedCrossRefGoogle Scholar
  8. 8.
    Morar B, Gresham D, Angelicheva D, Tournev I, Gooding R, Guergueltcheva V, Schmidt C, Abicht A, Lochmuller H, Tordai A, Kalmar L, Nagy M, Karcagi V, Jeanpierre M, Herczegfalvi A, Beeson D, Venkataraman V, Warwick Carter K, Reeve J, de Pablo R, Kucinskas V, Kalaydjieva L (2004) Mutation history of the roma/gypsies. Am J Hum Genet 75(4):596–609. doi:10.1086/424759 (S0002-9297(07)62711-6 [pii])PubMedCrossRefGoogle Scholar
  9. 9.
    Alusi SH, Worthington J, Glickman S, Bain PG (2001) A study of tremor in multiple sclerosis. Brain 124(Pt 4):720–730PubMedCrossRefGoogle Scholar
  10. 10.
    Lezak M (1995) Neuropsychological assessment. Oxford University Press, New YorkGoogle Scholar
  11. 11.
    Bellebaum C, Daum I (2007) Cerebellar involvement in executive control. Cerebellum 6(3):184–192. doi:10.1080/14734220601169707 (771178752 [pii])PubMedCrossRefGoogle Scholar
  12. 12.
    Laforce R Jr, Buteau JP, Bouchard JP, Rouleau GA, Bouchard RW, Dupre N (2010) Cognitive impairment in ARCA-1, a newly discovered pure cerebellar ataxia syndrome. Cerebellum 9(3):443–453. doi:10.1007/s12311-010-0184-7 PubMedCrossRefGoogle Scholar
  13. 13.
    Middleton FA, Strick PL (1994) Anatomical evidence for cerebellar and basal ganglia involvement in higher cognitive function. Science 266(5184):458–461PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Teodora Chamova
    • 1
  • Laura Florez
    • 2
  • Velina Guergueltcheva
    • 1
  • Margarita Raycheva
    • 1
  • Radka Kaneva
    • 3
  • Hanns Lochmüller
    • 4
  • Luba Kalaydjieva
    • 2
    • 6
  • Ivailo Tournev
    • 1
    • 5
  1. 1.Clinic of NeurologyUniversity Hospital “Alexandrovska”SofiaBulgaria
  2. 2.Molecular Genetics Laboratory, Western Australian Institute for Medical Research and Centre for Medical ResearchThe University of Western AustraliaPerthAustralia
  3. 3.Molecular Medicine CentreMedical University-SofiaSofiaBulgaria
  4. 4.Institute of Genetic MedicineNewcastle UniversityNewcastle upon TyneUK
  5. 5.Department of Cognitive Science and PsychologyNew Bulgarian UniversitySofiaBulgaria
  6. 6.Western Australian Institute for Medical ResearchNedlandsAustralia

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