Molecular and clinical study of a cohort of 110 Algerian patients with autosomal recessive ataxia

BMC Medical Genetics

Traki Benhassine⁴  Michel Koenig⁵  Meriem Tazir⁸  Malika Chaouch⁶  Samira Makri¹  Farida Ferrat⁶  Nathalie Drouot³  Jean Muller²  Tarik Hamadouche⁷  Lamia Ali Pacha⁸  Wahiba Hamza⁴ 

[1] Service de Neurologie, EHS Ali Aït Idir, Alger, Algeria;Laboratoire de Diagnostic Génétique, Hôpitaux Universitaires de Strasbourg, Strasbourg, France;Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/Université de Strasbourg UMR7104, INSERM U964, Illkirch, France;Laboratoire de Biologie Cellulaire et Moléculaire, Faculté des Sciences Biologiques, USTHB, Alger, Algeria;Laboratoire de Génétique de Maladies Rares, Institut Universitaire de Recherche Clinique, Université de Montpellier, CHU de Montpellier, Montpellier, France;Service de Neurologie, CHU Ben Aknoun, Alger, Algeria;Laboratoire de Biologie Moléculaire, Faculté des Sciences, UMBB, Boumerdes, Algeria;Laboratoire de Neurosciences, Université d’Alger 1, Alger, Algeria

关键词: Molecular analysis;    Cohort;    Algeria;    Autosomal recessive ataxias;    ARCA;   

Others  :  1220386
DOI  :  10.1186/s12881-015-0180-3

 received in 2014-11-15, accepted in 2015-05-29,  发布年份 2015

【 摘 要 】

Background

Autosomal recessive cerebellar ataxias (ARCA) are a complex group of neurodegenerative disorders with great genetic and phenotypic heterogeneity, over 30 genes/loci have been associated with more than 20 different clinical forms of ARCA. Genetic heterogeneity combined with highly variable clinical expression of the cerebellar symptoms and overlapping features complicate furthermore the etiological diagnosis of ARCA. The determination of the most frequent mutations and corresponding ataxias, as well as particular features specific to a population, are mandatory to facilitate and speed up the diagnosis process, especially when an appropriate treatment is available.

Methods

We explored 166 patients (115 families) refered to the neurology units of Algiers central hospitals (Algeria) with a cerebellar ataxia phenotype segregating as an autosomal recessive pattern of inheritance. Genomic DNA was extracted from peripheral blood samples and mutational screening was performed by PCR and direct sequencing or by targeted genomic capture and massive parallel sequencing of 57 genes associated with inherited cerebellar ataxia phenotypes.

Results

In this work we report the clinical and molecular results obtained on a large cohort of Algerian patients (110 patients/76 families) with genetically determined autosomal recessive ataxia, representing 9 different types of ARCA and 23 different mutations, including 6 novel ones. The five most common ARCA in this cohort were Friedreich ataxia, ataxia with isolated vitamin E deficiency, ataxia with oculomotor apraxia type 2, autosomal recessive spastic ataxia of Charlevoix-Saguenay and ataxia with oculomotor apraxia type 1.

Conclusion

We report here a large cohort of patients with genetically determined autosomal recessive ataxia and the first study of the genetic context of ARCA in Algeria. This study showed that in Algerian patients, the two most common types of ataxia (Friedreich ataxia and ataxia with isolated vitamin E deficiency) coexist with forms that may be less common or underdiagnosed. To refine the genotype/phenotype correlation in rare and heteregeneous diseases as autosomal recessive ataxias, more extensive epidemiological investigations and reports are necessary as well as more accurate and detailed clinical characterizations. The use of standardized clinical and molecular protocols would thus enable a better knowledge of the different forms of ARCA.

【 授权许可】

   
2015 Hamza et al.

【 图 表 】

Fig. 1.

【 参考文献 】

• [1]Palau F, Espinós C. Autosomal recessive cerebellar ataxias. Orphanet J Rare Dis. 2006; 1:47. BioMed Central Full Text
• [2]Fogel BL, Perlman S. Clinical features and molecular genetics of autosomal recessive cerebellar ataxias. Lancet Neurol. 2007; 6(3):245-57.
• [3]Harding AE. Classification of the hereditary ataxias and paraplegias. Lancet. 1983; 1(8334):1151-5.
• [4]Embiruçu EK, Martyn ML, Schlesinger D, Kok F. Autosomal recessive ataxias: 20 types, and counting. Arq Neuropsiquiatr. 2009; 67(4):1143-56.
• [5]Vermeer S, van de Warrenburg BP, Willemsen MA, Cluitmans M, Scheffer H, Kremer BP, Knoers NV. Autosomal recessive cerebellar ataxias: the current state of affairs. J Med Genet. 2011; 48(10):651-9.
• [6]Chun HH, Gatti RA. Ataxia-telangiectasia, an evolving phenotype. DNA Repair (Amst). 2004; 3(8-9):1187-96.
• [7]Ball LG, Xiao W. Molecular basis of ataxia telangiectasia and related diseases. Acta Pharmacol Sin. 2005; 26(8):897-907.
• [8]Van de Warrenburg BP, Sinke RJ, Kremer B. Recent advances in hereditary spinocerebellar ataxias. J Neuropathol Exp Neurol. 2005; 64(3):171-80.
• [9]Tazir M, Ali-Pacha L, M’Zahem A, Delaunoy JP, Fritsch M, Nouioua S, Benhassine T, Assami S, Grid D, Vallat JM, Hamri A, Koenig M. Ataxia with oculomotor apraxia type 2: a clinical and genetic study of 19 patients. J Neurol Sci. 2009; 278(1-2):77-81.
• [10]Vasli N, Böhm J, Le Gras S, Muller J, Pizot C, Jost B, Echaniz-Laguna A, Laugel V, Tranchant C, Bernard R, Plewniak F, Vicaire S, Levy N, Chelly J, Mandel JL, Biancalana V, Laporte J. Next generation sequencing for molecular diagnosis of neuromuscular diseases. Acta Neuropathol. 2012; 124(2):273-83.
• [11]Campuzano V, Montermini L, Moltò MD, Pianese L, Cossée M, Cavalcanti F, Monros E, Rodius F, Duclos F, Monticelli A, Zara F, Cañizares J, Koutnikova H, Bidichandani SI, Gellera C, Brice A, Trouillas P, De Michele G, Filla A, De Frutos R, Palau F, Patel PI, Di Donato S, Mandel JL, Cocozza S, Koenig M, Pandolfo M. Friedreich’s ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion. Science. 1996; 271(5254):1423-7.
• [12]Ouahchi K, Arita M, Kayden H, Hentati F, Ben Hamida M, Sokol R, Arai H, Inoue K, Mandel JL, Koenig M. Ataxia with isolated vitamin E deficiency is caused by mutations in the alpha-tocopherol transfer protein. Nat Genet. 1995; 9(2):141-5.
• [13]Micol R, Ben Slama L, Suarez F, Le Mignot L, Beauté J, Mahlaoui N, Dubois d’Enghien C, Laugé A, Hall J, Couturier J, Vallée L, Delobel B, Rivier F, Nguyen K, Billette De Villemeur T, Stephan JL, Bordigoni P, Bertrand Y, Aladjidi N, Pedespan JM, Thomas C, Pellier I, Koenig M, Hermine O, Picard C, Moshous D, Neven B, Lanternier F, Blanche S, Tardieu M, Debré M, Fischer A, Stoppa-Lyonnet D. Morbidity and mortality from ataxia-telangiectasia are associated with ATM genotype. J Allergy Clin Immunol. 2011; 128(2):382-9.
• [14]Pandolfo M, Pastore A. The pathogenesis of Friedreich ataxia and the structure and function of frataxin. J Neurol. 2009; 256 Suppl 1:9-17.
• [15]Anheim M, Tranchant C, Koenig M. The autosomal recessive cerebellar ataxias. N Engl J Med. 2012; 366(7):636-46.
• [16]Pandolfo M. Friedreich ataxia. Arch Neurol. 2008; 65(10):1296-303.
• [17]Palau F, Sevilla T. Genetics of peripheral neuropathies and hereditary ataxias. Neurologia. 1995; 10 Suppl 1:32-43.
• [18]Klockgether T, Zühlke C, Schulz JB, Bürk K, Fetter M, Dittmann H, Skalej M, Dichgans J. Friedreich’s ataxia with retained tendon reflexes: molecular genetics, clinical neurophysiology, and magnetic resonance imaging. Neurology. 1996; 46(1):118-21.
• [19]Dürr A, Cossee M, Agid Y, Campuzano V, Mignard C, Penet C, Mandel JL, Brice A, Koenig M. Clinical and genetic abnormalities in patients with Friedreich’s ataxia. N Engl J Med. 1996; 335(16):1169-75.
• [20]Harding AE. Friedreich’s ataxia: a clinical and genetic study of 90 families with an analysis of early diagnostic criteria and intrafamilial clustering of clinical features. Brain. 1981; 104(3):589-620.
• [21]Ribaï P, Pousset F, Tanguy ML, Rivaud-Pechoux S, Le Ber I, Gasparini F, Charles P, Béraud AS, Schmitt M, Koenig M, Mallet A, Brice A, Dürr A. Neurological, cardiological, and oculomotor progression in 104 patients with Friedreich ataxia during long-term follow-up. Arch Neurol. 2007; 64(4):558-64.
• [22]Cavalier L, Ouahchi K, Kayden HJ, Di Donato S, Reutenauer L, Mandel JL, Koenig M. Ataxia with isolated vitamin E deficiency: heterogeneity of mutations and phenotypic variability in a large number of families. Am J Hum Genet. 1998; 62(2):301-10.
• [23]El Euch-Fayache G, Bouhlal Y, Amouri R, Feki M, Hentati F. Molecular, clinical and peripheral neuropathy study of Tunisian patients with ataxia with vitamin E deficiency. Brain. 2014; 137(Pt 2):402-10.
• [24]Benomar A, Yahyaoui M, Meggouh F, Bouhouche A, Boutchich M, Bouslam N, Zaim A, Schmitt M, Belaidi H, Ouazzani R, Chkili T, Koenig M. Clinical comparison between AVED patients with 744 del A mutation and Friedreich ataxia with GAA expansion in 15 Moroccan families. J Neurol Sci. 2002; 198(1-2):25-9.
• [25]Mariotti C, Gellera C, Rimoldi M, Mineri R, Uziel G, Zorzi G, Pareyson D, Piccolo G, Gambi D, Piacentini S, Squitieri F, Capra R, Castellotti B, Di Donato S. Ataxia with isolated vitamin E deficiency: neurological phenotype, clinical follow-up and novel mutations in TTPA gene in Italian families. Neurol Sci. 2004; 25(3):130-7.
• [26]Gotoda T, Arita M, Arai H, Inoue K, Yokota T, Fukuo Y, Yazaki Y, Yamada N. Adult-onset spinocerebellar dysfunction caused by a mutation in the gene for the alpha-tocopherol-transfer protein. N Engl J Med. 1995; 333(20):1313-8.
• [27]Yokota T, Shiojiri T, Gotoda T. Friedreich-like ataxia with retinitis pigmentosa caused by the His101Gln mutation of a-tocopherol transfer protein gene. Ann Neurol. 1997; 41(6):826-32.
• [28]Anheim M, Fleury M, Monga B, Laugel V, Chaigne D, Rodier G, Ginglinger E, Boulay C, Courtois S, Drouot N, Fritsch M, Delaunoy JP, Stoppa-Lyonnet D, Tranchant C, Koenig M. Epidemiological, clinical, paraclinical and molecular study of a cohort of 102 patients affected with autosomal recessive progressive cerebellar ataxia from Alsace, Eastern France: implications for clinical management. Neurogenetics. 2010; 11(1):1-12.
• [29]Kayden HJ. The neurologic syndrome of vitamin E deficiency: a significant cause of ataxia. Neurology. 1993; 3(11):2167-9.
• [30]Gabsi S, Gouider-Khouja N, Belal S, Fki M, Kefi M, Turki I, Ben Hamida M, Kayden H, Mebazaa R, Hentati F. Effect of vitamin E supplementation in patients with ataxia with vitamin E deficiency. Eur J Neurol. 2001; 8(5):477-81.
• [31]Müller KI, Bekkelund SI: Epilepsy in a patient with ataxia caused by vitamin E deficiency. BMJ Case Rep 2011. doi:10.1136/bcr.01.2011.3728.
• [32]Moreira MC, Klur S, Watanabe M, Németh AH, Le Ber I, Moniz JC, Tranchant C, Aubourg P, Tazir M, Schöls L, Pandolfo M, Schulz JB, Pouget J, Calvas P, Shizuka-Ikeda M, Shoji M, Tanaka M, Izatt L, Shaw CE, M’Zahem A, Dunne E, Bomont P, Benhassine T, Bouslam N, Stevanin G, Brice A, Guimarães J, Mendonça P, Barbot C, Coutinho P, Sequeiros J, Dürr A, Warter JM, Koenig M. Senataxin, the ortholog of a yeast RNA helicase, is mutant in ataxia-ocular apraxia 2. Nat Genet. 2004; 36(3):225-7.
• [33]Le Ber I, Bouslam N, Rivaud-Péchoux S, Guimarães J, Benomar A, Chamayou C, Goizet C, Moreira MC, Klur S, Yahyaoui M, Agid Y, Koenig M, Stevanin G, Brice A, Dürr A. Frequency and phenotypic spectrum of ataxia with oculomotor apraxia 2: a clinical and genetic study in 18 patients. Brain. 2004; 127(Pt 4):759-67.
• [34]Duquette A, Roddier K, McNabb-Baltar J, Gosselin I, St-Denis A, Dicaire MJ, Loisel L, Labuda D, Marchand L, Mathieu J, Bouchard JP, Brais B. Mutations in senataxin responsible for Quebec cluster of ataxia with neuropathy. Ann Neurol. 2005; 57(3):408-14.
• [35]Criscuolo C, Chessa L, Di Giandomenico S, Mancini P, Saccà F, Grieco GS, Piane M, Barbieri F, De Michele G, Banfi S, Pierelli F, Rizzuto N, Santorelli FM, Gallosti L, Filla A, Casali C. Ataxia with oculomotor apraxia type 2: a clinical, pathologic, and genetic study. Neurology. 2006; 66(8):1207-10.
• [36]El Euch-Fayache G, Lalani I, Amouri R, Turki I, Ouahchi K, Hung WY, Belal S, Siddique T, Hentati F. Phenotypic features and genetic findings in sacsin-related autosomal recessive ataxia in Tunisia. Arch Neurol. 2003; 60(7):982-8.
• [37]Bouchard JP, Richter A, Mathieu J, Brunet D, Hudson TJ, Morgan K, Melançon SB. Autosomal recessive spastic ataxia of Charlevoix-Saguenay. Neuromuscul Disord. 1998; 8(7):474-9.
• [38]Bouchard JP, Barbeau A, Bouchard R, Bouchard RW. Autosomal recessive spastic ataxia of Charlevoix-Saguenay. Can J Neurol Sci. 1978; 5(1):61-9.
• [39]Vingolo EM, Di Fabio R, Salvatore S, Grieco G, Bertini E, Leuzzi V, Nesti C, Filla A, Tessa A, Pierelli F, Santorelli FM, Casali C. Myelinated retinal fibers in autosomal recessive spastic ataxia of Charlevoix-Saguenay. Eur J Neurol. 2011; 18(9):1187-90.
• [40]Baets J, Deconinck T, Smets K, Goossens D, Van den Bergh P, Dahan K, Schmedding E, Santens P, Rasic VM, Van Damme P, Robberecht W, De Meirleir L, Michielsens B, Del-Favero J, Jordanova A, De Jonghe P. Mutations in SACS cause atypical and late-onset forms of ARSACS. Neurology. 2010; 75(13):1181-8.
• [41]Vermeer S, Meijer RP, Pijl BJ, Timmermans J, Cruysberg JR, Bos MM, Schelhaas HJ, van de Warrenburg BP, Knoers NV, Scheffer H, Kremer B. ARSACS in the Dutch population: a frequent cause of early-onset cerebellar ataxia. Neurogenetics. 2008; 9(3):207-14.
• [42]Barbot C, Coutinho P, Chorão R, Ferreira C, Barros J, Fineza I, Dias K, Monteiro J, Guimarães A, Mendonça P, Do Céu Moreira M, Sequeiros J. Recessive ataxia with ocular apraxia: review of 22 Portuguese patients. Arch Neurol. 2001; 58(2):201-5.
• [43]Date H, Onodera O, Tanaka H, Iwabuchi K, Uekawa K, Igarashi S, Koike R, Hiroi T, Yuasa T, Awaya Y, Sakai T, Takahashi T, Nagatomo H, Sekijima Y, Kawachi I, Takiyama Y, Nishizawa M, Fukuhara N, Saito K, Sugano S, Tsuji S. Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is caused by mutations in a new HIT superfamily gene. Nat Genet. 2001; 29(2):184-8.
• [44]Moreira MC, Barbot C, Tachi N, Kozuka N, Uchida E, Gibson T, Mendonça P, Costa M, Barros J, Yanagisawa T, Watanabe M, Ikeda Y, Aoki M, Nagata T, Coutinho P, Sequeiros J, Koenig M. The gene mutated in ataxia-ocular apraxia 1 encodes the new HIT/Zn-finger protein aprataxin. Nat Genet. 2001; 29(2):189-93.
• [45]Le Ber I, Moreira MC, Rivaud-Péchoux S, Chamayou C, Ochsner F, Kuntzer T, Tardieu M, Saïd G, Habert MO, Demarquay G, Tannier C, Beis JM, Brice A, Koenig M, Dürr A. Cerebellar ataxia with oculomotor apraxia type 1: clinical and genetic studies. Brain. 2003; 126(Pt 12):2761-2672.
• [46]Amouri R, Moreira MC, Zouari M, El Euch G, Barhoumi C, Kefi M, Belal S, Koenig M, Hentati F. Aprataxin gene mutations in Tunisian families. Neurology. 2004; 63(5):928-9.
• [47]Castellotti B, Mariotti C, Rimoldi M, Fancellu R, Plumari M, Caimi S, Uziel G, Nardocci N, Moroni I, Zorzi G, Pareyson D, Di Bella D, Di Donato S, Taroni F, Gellera C. Ataxia with oculomotor apraxia type1 (AOA1): novel and recurrent aprataxin mutations, coenzyme Q10 analyses, and clinical findings in Italian patients. Neurogenetics. 2011; 12(3):193-201.
• [48]Tranchant C, Fleury M, Moreira MC, Koenig M, Warter JM. Phenotypic variability of aprataxin gene mutations. Neurology. 2003; 60(5):868-70.
• [49]Lagier-Tourenne C, Tazir M, López LC, Quinzii CM, Assoum M, Drouot N, Busso C, Makri S, Ali-Pacha L, Benhassine T, Anheim M, Lynch DR, Thibault C, Plewniak F, Bianchetti L, Tranchant C, Poch O, DiMauro S, Mandel JL, Barros MH, Hirano M, Koenig M. ADCK3, an ancestral kinase, is mutated in a form of recessive ataxia associated with coenzyme Q10 deficiency. Am J Hum Genet. 2008; 82(3):661-72.
• [50]Horvath R, Czermin B, Gulati S, Demuth S, Houge G, Pyle A, Dineiger C, Blakely EL, Hassani A, Foley C, Brodhun M, Storm K, Kirschner J, Gorman GS, Lochmüller H, Holinski-Feder E, Taylor RW, Chinnery PF. Adult-onset cerebellar ataxia due to mutations in CABC1/ADCK3. J Neurol Neurosurg Psychiatry. 2012; 83(2):174-8.
• [51]Mignot C, Apartis E, Dürr A, Marques Lourenço C, Charles P, Devos D, Moreau C, de Lonlay P, Drouot N, Burglen L, Kempf N, Nourisson E, Chantot-Bastaraud S, Lebre AS, Rio M, Chaix Y, Bieth E, Roze E, Bonnet I, Canaple S, Rastel C, Brice A, Rötig A, Desguerre I, Tranchant C, Koenig M, Anheim M. Phenotypic variability in ARCA2 and identification of a core ataxic phenotype with slow progression. Orphanet J Rare Dis. 2013; 8:173. BioMed Central Full Text
• [52]Gerards M, van den Bosch B, Calis C, Schoonderwoerd K, van Engelen K, Tijssen M, de Coo R, van der Kooi A, Smeets H. Nonsense mutations in CABC1/ADCK3 cause progressive cerebellar ataxia and atrophy. Mitochondrion. 2010; 10(5):510-5.
• [53]Mollet J, Delahodde A, Serre V, Chretien D, Schlemmer D, Lombes A, Boddaert N, Desguerre I, de Lonlay P, de Baulny HO, Munnich A, Rötig A. CABC1 gene mutations cause ubiquinone deficiency with cerebellar ataxia and seizures. Am J Hum Genet. 2008; 82(3):623-30.
• [54]Chen DH, Naydenov A, Blankman JL, Mefford HC, Davis M, Sul Y, Barloon AS, Bonkowski E, Wolff J, Matsushita M, Smith C, Cravatt BF, Mackie K, Raskind WH, Stella N, Bird TD. Two novel mutations in ABHD12: expansion of the mutation spectrum in PHARC and assessment of their functional effects. Hum Mutat. 2013; 34(12):1672-8.
• [55]Nishiguchi KM, Avila-Fernandez A, van Huet RA, Corton M, Pérez-Carro R, Martín-Garrido E, López-Molina MI, Blanco-Kelly F, Hoefsloot LH, van Zelst-Stams WA, García-Ruiz PJ, Del Val J, Di Gioia SA, Klevering BJ, van de Warrenburg BP, Vazquez C, Cremers FP, García-Sandoval B, Hoyng CB, Collin RW, Rivolta C, Ayuso C. Exome sequencing extends the phenotypic spectrum for ABHD12 mutations: From syndromic to nonsyndromic retinal degeneration. Ophtalmol. 2014; 121(8):1620-7.
• [56]Fiskerstrand T, H’mida-Ben Brahim D, Johansson S, M’zahem A, Haukanes BI, Drouot N, Zimmermann J, Cole AJ, Vedeler C, Bredrup C, Assoum M, Tazir M, Klockgether T, Hamri A, Steen VM, Boman H, Bindoff LA, Koenig M, Knappskog PM. Mutations in ABHD12 cause the neurodegenerative disease PHARC: an inborn error of endocannabinoid metabolism. Am J Hum Genet. 2010; 87(3):410-7.
• [57]Gros-Louis F, Dupré N, Dion P, Fox MA, Laurent S, Verreault S, Sanes JR, Bouchard JP, Rouleau GA. Mutations in SYNE1 lead to a newly discovered form of autosomal recessive cerebellar ataxia. Nat Genet. 2007; 39(1):80-5.
• [58]Dupré N, Gros-Louis F, Chrestian N, Verreault S, Brunet D, de Verteuil D, Brais B, Bouchard JP, Rouleau GA. Clinical and genetic study of autosomal recessive cerebellar ataxia type 1. Ann Neurol. 2007; 62(1):93-8.
• [59]Dupré N, Bouchard JP, Gros-Louis F, Rouleau GA. Mutations in SYNE-1 lead to a newly discovered form of autosomal recessive cerebellar ataxia. Med Sci (Paris). 2007; 23(3):261-2.
• [60]Komiyama A, Nonaka I, Hirayama K. Muscle pathology in Marinesco-Sjögren syndrome. J Neurol Sci. 1989; 89(1):103-13.
• [61]Lagier-Tourenne C, Tranebaerg L, Chaigne D, Gribaa M, Dollfus H, Silvestri G, Bétard C, Warter JM, Koenig M. Homozygosity mapping of Marinesco-Sjögren syndrome to 5q31. Eur J Hum Genet. 2003; 11(10):770-8.
• [62]Farah S, Sabry MA, Khuraibet AJ, Anim JT, Quasrawi B, Al-Khatam S, Al-Busairi W, Hussein JM, Khan RA, Al-Awadi SA. Marinesco-Sjogren syndrome in a Bedouin family. Acta Neurol Scand. 1997; 96(6):387-91.
• [63]Anttonen AK, Mahjneh I, Hämäläinen RH, Lagier-Tourenne C, Kopra O, Waris L, Anttonen M, Joensuu T, Kalimo H, Paetau A, Tranebjaerg L, Chaigne D, Koenig M, Eeg-Olofsson O, Udd B, Somer M, Somer H, Lehesjoki AE. The gene disrupted in Marinesco-Sjögren syndrome encodes SIL1, an HSPA5 cochaperone. Nat Genet. 2005; 37(12):1309-11.
• [64]Nicolaou P, Georghiou A, Votsi C, Middleton LT, Zamba-Papanicolaou E, Christodoulou K. A novel c.5308_5311delGAGA mutation in Senataxin in a Cypriot family with an autosomal recessive cerebellarataxia. BMC Med Genet. 2008; 9:28. BioMed Central Full Text
• [65]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. Molecular diagnosis of known recessive ataxias by homozygosity mapping with SNP arrays. J Neurol. 2011; 258(1):56-67.