Abstract
Fabry disease (FD) is an X-linked monogenic disorder caused by mutations in the GLA gene which leads to a deficiency of the functionally active lysosomal α-galactosidase A enzyme. Here, we report on a family of five members: unaffected parents, one unaffected son, and another son and daughter both carrying the same mutation (p.G138E) in the GLA gene. Genotype analysis using intragenic GLA markers confirmed the maternal origin of the mutation. The affected son and daughter carried the same mutation; however, it was not detected in the peripheral blood, buccal cells, and urinary sediment cells of their mother. Moreover, the unaffected son without the alteration in the GLA gene carried the same maternal chromosome X (disease-associated) haplotype. To the best of our knowledge, this study represents the first case of maternal germline mosaicism in FD.
References
Germain DP (2010) Fabry disease. Orphanet J Rare Dis 5:30
Ortiz A, Germain DP, Desnick RJ, Politei J, Mauer M, Burlina A, Eng C, Hopkin RJ, Laney D, Linhart A, Waldek S, Wallace E, Weidemann F, Wilcox WR (2018) Fabry disease revisited: management and treatment recommendations for adult patients. Mol Genet Metab 123:416–427
Smid BE, van der Tol L, Biegstraaten M, Linthorst GE, Hollak CE, Poorthuis BJ (2015) Plasma globotriaosylsphingosine in relation to phenotypes of Fabry disease. J Med Genet 52:262–268
Echevarria L, Benistan K, Toussaint A, Dubourg O, Hagege AA, Eladari D, Jabbour F, Beldjord C, De Mazancourt P, Germain DP (2016) X-chromosome inactivation in female patients with Fabry disease. Clin Genet 89:44–54
Gal A, Hughes DA, Winchester B (2011) Toward a consensus in the laboratory diagnostics of Fabry disease - recommendations of a European expert group. J Inherit Metab Dis 34:509–514
Dobrovolný R, Dvoráková L, Ledvinová J, Magage S, Bultas J, Lubanda JC, Poupetová H, Elleder M, Karetová D, Hrebícek M (2005) Recurrence of Fabry disease as a result of paternal germline mosaicism for alpha-galactosidase a gene mutation. Am J Med Genet A 134:84–87
Polo G, Burlina AP, Kolamunnage TB, Zampieri M, Dionisi-Vici C, Strisciuglio P, Zaninotto M, Plebani M, Burlina AB (2017) Diagnosis of sphingolipidoses: a new simultaneous measurement of lysosphingolipids by LC-MS/MS. Clin Chem Lab Med 55:403–414
Ishii S, Nakao S, Minamikawa-Tachino R, Desnick RJ, Fan JQ (2002) Alternative splicing in the alpha-galactosidase A gene: increased exon inclusion results in the Fabry cardiac phenotype. Am J Hum Genet 70:994–1002
Bono C, Nuzzo D, Albeggiani G, Zizzo C, Francofonte D, Iemolo F, Sanzaro E, Duro G (2011) Genetic screening of Fabry patients with EcoTILLING and HRM technology. BMC Res Notes 4:323
Germain DP, Shabbeer J, Cotigny S, Desnick RJ (2002) Fabry disease: twenty novel alpha-galactosidase A mutations and genotype-phenotype correlations in classical and variant phenotypes. Mol Med 8:306–312
Ferri L, Guido C, la Marca G, Malvagia S, Cavicchi C, Fiumara A, Barone R, Parini R, Antuzzi D, Feliciani C, Zampetti A, Manna R, Giglio S, Della Valle CM, Wu X, Valenzano KJ, Benjamin R, Donati MA, Guerrini R, Genuardi M, Morrone A (2012) Fabry disease: polymorphic haplotypes and a novel missense mutation in the GLA gene. Clin Genet 81(3):224–233
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We are grateful to the patients and their family for their kind collaboration.
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Pianese, L., Fortunato, A., Silvestri, S. et al. Maternal germline mosaicism in Fabry disease. Neurol Sci 40, 1279–1281 (2019). https://doi.org/10.1007/s10072-019-03754-1
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DOI: https://doi.org/10.1007/s10072-019-03754-1