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

A multicenter Fabry Registry study

Dominique P. Germain, Eva Brand, Alessandro Burlina, Franco Cecchi, Scott C. Garman, Judy Kempf, Dawn A. Laney, Aleš Linhart, L. Máródi, Kathy Nicholls, Alberto Ortiz, Federico Pieruzzi, Suma P. Shankar, Stephen Waldek, Christoph Wanner, Ana Jovanovic

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish
JournalMolecular Genetics and Genomic Medicine
DOIs
Publication statusAccepted/In press - Jan 1 2018

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Fabry Disease
Registries
Mutation
Kidney
Natural History
Glomerular Filtration Rate
Phenotype

Keywords

  • Cardiac variant
  • Fabry disease
  • GLA
  • P.Asn215Ser
  • P.N215S
  • Phenotype

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Phenotypic characteristics of the p.Asn215Ser (p.N215S) GLA mutation in male and female patients with Fabry disease : A multicenter Fabry Registry study. / Germain, Dominique P.; Brand, Eva; Burlina, Alessandro; Cecchi, Franco; Garman, Scott C.; Kempf, Judy; Laney, Dawn A.; Linhart, Aleš; Máródi, L.; Nicholls, Kathy; Ortiz, Alberto; Pieruzzi, Federico; Shankar, Suma P.; Waldek, Stephen; Wanner, Christoph; Jovanovic, Ana.

In: Molecular Genetics and Genomic Medicine, 01.01.2018.

Research output: Contribution to journalArticle

Germain, DP, Brand, E, Burlina, A, Cecchi, F, Garman, SC, Kempf, J, Laney, DA, Linhart, A, Máródi, L, Nicholls, K, Ortiz, A, Pieruzzi, F, Shankar, SP, Waldek, S, Wanner, C & Jovanovic, A 2018, 'Phenotypic characteristics of the p.Asn215Ser (p.N215S) GLA mutation in male and female patients with Fabry disease: A multicenter Fabry Registry study', Molecular Genetics and Genomic Medicine. https://doi.org/10.1002/mgg3.389
Germain, Dominique P. ; Brand, Eva ; Burlina, Alessandro ; Cecchi, Franco ; Garman, Scott C. ; Kempf, Judy ; Laney, Dawn A. ; Linhart, Aleš ; Máródi, L. ; Nicholls, Kathy ; Ortiz, Alberto ; Pieruzzi, Federico ; Shankar, Suma P. ; Waldek, Stephen ; Wanner, Christoph ; Jovanovic, Ana. / Phenotypic characteristics of the p.Asn215Ser (p.N215S) GLA mutation in male and female patients with Fabry disease : A multicenter Fabry Registry study. In: Molecular Genetics and Genomic Medicine. 2018.
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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.",
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T1 - Phenotypic characteristics of the p.Asn215Ser (p.N215S) GLA mutation in male and female patients with Fabry disease

T2 - A multicenter Fabry Registry study

AU - Germain, Dominique P.

AU - Brand, Eva

AU - Burlina, Alessandro

AU - Cecchi, Franco

AU - Garman, Scott C.

AU - Kempf, Judy

AU - Laney, Dawn A.

AU - Linhart, Aleš

AU - Máródi, L.

AU - Nicholls, Kathy

AU - Ortiz, Alberto

AU - Pieruzzi, Federico

AU - Shankar, Suma P.

AU - Waldek, Stephen

AU - Wanner, Christoph

AU - Jovanovic, Ana

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

KW - Cardiac variant

KW - Fabry disease

KW - GLA

KW - P.Asn215Ser

KW - P.N215S

KW - Phenotype

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