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Author Notes:

Correspondence: Dominique P. Germain, Division of Medical Genetics, University of Versailles - St Quentin en Yvelines, UFR des Sciences de la Sante Simone Veil, Montigny, France. Email: dominique.germain@inserm.fr

The authors thank the patients who agreed to participate in the Fabry Registry.

The authors were responsible for all content and editorial decisions and received no honoraria related to the development of this publication.

See publication for full list of disclosures.

Subjects:

Research Funding:

The authors received editorial/writing support in the preparation of this manuscript from Tom Rouwette of Excerpta Medica, funded by Sanofi Genzyme, and Hans Ebels of Sanofi Genzyme.

D.P. Germain was supported by the Plan National Maladies Rares of the French Ministry of Health and A. Ortiz was supported by Intensificación FIS and FEDER Funds REDINREN RD012/0021.

The Fabry Registry is sponsored by Sanofi Genzyme.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Genetics & Heredity
  • cardiac variant
  • Fabry disease
  • GLA
  • p. Asn215Ser
  • p. N215S
  • phenotype
  • ALPHA-GALACTOSIDASE-A
  • NATURAL-HISTORY DATA
  • ATYPICAL VARIANT
  • CARDIAC VARIANT
  • POINT MUTATIONS
  • OUTCOME SURVEY
  • GENE
  • MANIFESTATIONS
  • CARDIOMYOPATHY
  • IDENTIFICATION

Phenotypic characteristics of the p.Asn215Ser (p.N215S) GLA mutation in male and female patients with Fabry disease: A multicenter Fabry Registry study

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Journal Title:

Molecular Genetics and Genomic Medicine

Volume:

Volume 6, Number 4

Publisher:

, Pages 492-503

Type of Work:

Article | Final Publisher PDF

Abstract:

Background: The p.Asn215Ser or p.N215S GLA variant has been associated with late-onset cardiac variant of Fabry disease. Methods: To expand on the scarce phenotype data, we analyzed natural history data from 125 p.N215S patients (66 females, 59 males) enrolled in the Fabry Registry (NCT00196742) and compared it with data from 401 patients (237 females, 164 males) harboring mutations associated with classic Fabry disease. We evaluated interventricular septum thickness (IVST), left ventricular posterior wall thickness (LVPWT), estimated glomerular filtration rate and severe clinical events. Results: In p.N215S males, mildly abnormal mean IVST and LVPWT values were observed in patients aged 25–34 years, and values gradually increased with advancing age. Mean values were similar to those of classic males. In p.N215S females, these abnormalities occurred primarily in patients aged 55–64 years. Severe clinical events in p.N215S patients were mainly cardiac (males 31%, females 8%) while renal and cerebrovascular events were rare. Renal impairment occurred in 17% of p.N215S males (mostly in patients aged 65–74 years), and rarely in females (3%). Conclusion: p.N215S is a disease-causing mutation with severe clinical manifestations found primarily in the heart. Cardiac involvement may become as severe as in classic Fabry patients, especially in males.

Copyright information:

© 2018 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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