Phenotypic variation of FXN compound heterozygotes in a Friedreich ataxia cohort.
Journal
Annals of clinical and translational neurology
ISSN: 2328-9503
Titre abrégé: Ann Clin Transl Neurol
Pays: United States
ID NLM: 101623278
Informations de publication
Date de publication:
23 Feb 2024
23 Feb 2024
Historique:
revised:
24
01
2024
received:
13
12
2023
accepted:
09
02
2024
medline:
24
2
2024
pubmed:
24
2
2024
entrez:
24
2
2024
Statut:
aheadofprint
Résumé
Most individuals with Friedreich ataxia (FRDA) have homozygous GAA triplet repeat expansions in the FXN gene, correlating with a typical phenotype of ataxia and cardiomyopathy. A minority are compound heterozygotes carrying a GAA expansion on one allele and a mutation on the other. The study aim was to examine phenotypic variation among compound heterozygotes. Data on FXN mutations were obtained from the Friedreich Ataxia Clinical Outcome Measures Study (FA-COMS). We compared clinical features in a single-site FA-COMS cohort of 51 compound heterozygous and 358 homozygous patients, including quantitative measures of cardiac, neurologic, and visual disease progression. Non-GAA repeat mutations were associated with reduced cardiac disease, and patients with minimal/no function mutations otherwise had a typical FRDA phenotype but with significantly more severe progression. The partial function mutation group was characterized by relative sparing of bulbar and upper limb function, as well as particularly low cardiac involvement. Other clinical features in this group, including optic atrophy and diabetes mellitus, varied widely depending on the specific type of partial function mutation. These data support that the typical FRDA phenotype is driven by frataxin deficiency, especially severe in compound heterozygotes with minimal/no function mutations, whereas the heterogeneous presentations of those with partial function mutations may indicate other contributing factors to FRDA pathogenesis.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Friedreich Ataxia Research Alliance
Informations de copyright
© 2024 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.
Références
Pandolfo M. Friedreich ataxia. Handb Clin Neurol. 2012;103:275-294.
Keita M, McIntyre K, Rodden LN, Schadt K, Lynch DR. Friedreich ataxia: clinical features and new developments. Neurodegener Dis Manag. 2022;12(5):267-283.
Delatycki MB, Corben LA. Clinical features of Friedreich ataxia. J Child Neurol. 2012;27(9):1133-1137.
De Castro M, García-Planells J, Monrós E, et al. Genotype and phenotype analysis of Friedreich's ataxia compound heterozygous patients. Hum Genet. 2000;106(1):86-92.
Galea CA, Huq A, Lockhart PJ, et al. Compound heterozygous FXN mutations and clinical outcome in friedreich ataxia. Ann Neurol. 2016;79(3):485-495.
Gellera C, Castellotti B, Mariotti C, et al. Frataxin gene point mutations in Italian Friedreich ataxia patients. Neurogenetics. 2007;8(4):289-299.
Pook M, Al-Mahdawi S, Thomas N, et al. Identification of three novel frameshift mutations in patients with Friedreich's ataxia. J Med Genet. 2000;37(11):e38.
Forrest SM, Knight M, Delatycki MB, et al. The correlation of clinical phenotype in Friedreich ataxia with the site of point mutations in the FRDA gene. Neurogenetics. 1998;1(4):253-257.
Cossée M, Dürr A, Schmitt M, et al. Friedreich's ataxia: point mutations and clinical presentation of compound heterozygotes. Ann Neurol. 1999;45(2):200-206.
Parkinson MH, Boesch S, Nachbauer W, Mariotti C, Giunti P. Clinical features of Friedreich's ataxia: classical and atypical phenotypes. J Neurochem. 2013;126(Suppl 1):103-117.
McCormack ML, Guttmann RP, Schumann M, et al. Frataxin point mutations in two patients with Friedreich's ataxia and unusual clinical features. J Neurol Neurosurg Psychiatry. 2000;68(5):661-664.
De Michele G, Filla A, Cavalcanti F, et al. Atypical Friedreich ataxia phenotype associated with a novel missense mutation in the X25 gene. Neurology. 2000;54(2):496-499.
Candayan A, Yunisova G, Çakar A, et al. The first biallelic missense mutation in the FXN gene in a consanguineous Turkish family with Charcot-Marie-tooth-like phenotype. Neurogenetics. 2020;21(1):73-78.
Salisachs P, Findley LJ, Codina M, Torre PL, Martinez-Lage JM. A case of Charcot-Marie-Tooth disease mimicking Friedreich's ataxia: is there any association between friedreich's ataxia and Charcot-Marie-Tooth disease? Can J Neurol Sci. 1982;9(2):99-103.
Panas M, Kalfakis N, Karadima G, Davaki P, Vassilopoulos D. Friedreich's ataxia mimicking hereditary motor and sensory neuropathy. J Neurol. 2002;249(11):1583-1586.
Campuzano V, Montermini L, Lutz Y, et al. Frataxin is reduced in Friedreich ataxia patients and is associated with mitochondrial membranes. Hum Mol Genet. 1997;6(11):1771-1780.
Deutsch EC, Santani AB, Perlman SL, et al. A rapid, noninvasive immunoassay for frataxin: utility in assessment of Friedreich ataxia. Mol Genet Metab. 2010;101(2-3):238-245.
Clark E, Butler JS, Isaacs CJ, Napierala M, Lynch DR. Selected missense mutations impair frataxin processing in Friedreich ataxia. Ann Clin Transl Neurol. 2017;4(8):575-584.
Shan Y, Napoli E, Cortopassi G. Mitochondrial frataxin interacts with ISD11 of the NFS1/ISCU complex and multiple mitochondrial chaperones. Hum Mol Genet. 2007;16(8):929-941.
Condò I, Malisan F, Guccini I, Serio D, Rufini A, Testi R. Molecular control of the cytosolic aconitase/IRP1 switch by extramitochondrial frataxin. Hum Mol Genet. 2010;19(7):1221-1229.
Dong YN, Mesaros C, Xu P, et al. Frataxin controls ketone body metabolism through regulation of OXCT1. PNAS Nexus. 2022;1(3):pgac142.
Puglisi R. Protein mutations and stability, a link with disease: the case study of frataxin. Biomedicine. 2022;10(2):425.
Clark E, Strawser C, Schadt K, Lynch DR. Identification of a novel missense mutation in Friedreich's ataxia -FXNW 168R. Ann Clin Transl Neurol. 2019;6(4):812-816.
Tsai CL, Bridwell-Rabb J, Barondeau DP. Friedreich's ataxia variants I154F and W155R diminish frataxin-based activation of the iron-sulfur cluster assembly complex. Biochemistry. 2011;50(29):6478-6487.
Li H, Gakh O, Smith DY, et al. Partial function mutations linked to Friedreich ataxia have different but synergistic effects on mitochondrial frataxin isoforms. J Biol Chem. 2013;288(6):4116-4127.
Patel M, Isaacs CJ, Seyer L, et al. Progression of Friedreich ataxia: quantitative characterization over 5 years. Ann Clin Transl Neurol. 2016;3(9):684-694.
Lazaropoulos M, Dong Y, Clark E, et al. Frataxin levels in peripheral tissue in Friedreich ataxia. Ann Clin Transl Neurol. 2015;2(8):831-842.
Chaulin AM. Gender specificities of cardiac troponin serum levels: from formation mechanisms to the diagnostic role in case of acute coronary syndrome. Life (Basel). 2023;13(2):267.
Rodden LN, McIntyre K, Keita M, et al. Retinal hypoplasia and degeneration result in vision loss in Friedreich ataxia. Ann Clin Transl Neurol. 2023;10(8):1397-1406.
Rummey C, Corben LA, Delatycki M, et al. Natural history of Friedreich's ataxia: heterogeneity of neurological progression and consequences for clinical trial design. Neurology. 2022;99(14):e1499-e1510.
Rodden LN, Rummey C, Kessler S, Wilson RB, Lynch DR. A novel metric for predicting severity of disease features in Friedreich's ataxia. Mov Disord. 2023;38(6):970-977.
Labuda M, Poirier J, Pandolfo M. A missense mutation (W155R) in an American patient with Friedreich ataxia. Hum Mutat. 1999;13:506.
Diehl B, Lee MS, Reid JR, Nielsen CD, Natowicz MR. Atypical, perhaps under-recognized? An unusual phenotype of Friedreich ataxia. Neurogenetics. 2010;11(2):261-265.
Bogdanova-Mihaylova P, Plapp HM, Chen H, et al. Longitudinal assessment using optical coherence tomography in patients with Friedreich's ataxia. Tomography. 2021;7(4):915-931.
Pousset F, Legrand L, Monin ML, et al. A 22-year follow-up study of long-term cardiac outcome and predictors of survival in Friedreich ataxia. JAMA Neurol. 2015;72(11):1334-1341.
Tsou AY, Paulsen EK, Lagedrost SJ, et al. Mortality in Friedreich ataxia. J Neurol Sci. 2011;307(1-2):46-49.
Weidemann F, Rummey C, Bijnens B, et al. The heart in Friedreich ataxia: definition of cardiomyopathy, disease severity, and correlation with neurological symptoms. Circulation. 2012;125(13):1626-1634.
Hanson E, Sheldon M, Pacheco B, Alkubeysi M, Raizada V. Heart disease in Friedreich's ataxia. World J Cardiol. 2019;11(1):1-12.
Payne RM, Wagner GR. Cardiomyopathy in Friedreich ataxia: clinical findings and research. J Child Neurol. 2012;27(9):1179-1186.
Becker AB, Qian J, Gelman BB, Yang M, Bauer P, Koeppen AH. Heart and nervous system pathology in compound heterozygous Friedreich ataxia. J Neuropathol Exp Neurol. 2017;76(8):665-675.
Schadt KA, Friedman LS, Regner SR, Mark GE, Lynch DR, Lin KY. Cross-sectional analysis of electrocardiograms in a large heterogeneous cohort of Friedreich ataxia subjects. J Child Neurol. 2012;27(9):1187-1192.
Friedman LS, Schadt KA, Regner SR, et al. Elevation of serum cardiac troponin I in a cross-sectional cohort of asymptomatic subjects with Friedreich ataxia. Int J Cardiol. 2013;167(4):1622-1624.
Legrand L, Maupain C, Monin ML, et al. Significance of NT-proBNP and high-sensitivity troponin in Friedreich ataxia. J Clin Med. 2020;9(6):1630.
Regner SR, Lagedrost SJ, Plappert T, et al. Analysis of echocardiograms in a large heterogeneous cohort of patients with friedreich ataxia. Am J Cardiol. 2012;109(3):401-405.
Payne RM. Cardiovascular research in Friedreich ataxia: unmet needs and opportunities. JACC Basic Transl Sci. 2022;7(12):1267-1283.
Weidemann F, Liu D, Hu K, et al. The cardiomyopathy in Friedreich's ataxia - new biomarker for staging cardiac involvement. Int J Cardiol. 2015;194:50-57.
Legrand L, Weinsaft JW, Pousset F, et al. Characterizing cardiac phenotype in Friedreich's ataxia: the CARFA study. Arch Cardiovasc Dis. 2022;115(1):17-28.
Legrand L, Heuze C, Diallo A, et al. Prognostic value of longitudinal strain and ejection fraction in Friedreich's ataxia. Int J Cardiol. 2021;330:259-265.
Mejia E, Lynch A, Hearle P, et al. Ectopic burden via Holter monitors in Friedreich ataxia. Pediatr Neurol. 2021;117:29-33.