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Renal globotriaosylceramide deposits for Fabry disease linked to uncertain pathogenicity gene variant c.352C>T/p.Arg118Cys: A family study
BACKGROUND: Fabry disease (FD) has an extensive phenotypic expression associated with GLA gene variants. The GLA gene variant c.352C>T/p.Arg118Cys was considered with uncertain pathogenicity because of the finding of high residual alpha‐galactosidase A (α‐Gal A) enzyme activity, the absence of Me...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6825844/ https://www.ncbi.nlm.nih.gov/pubmed/31566927 http://dx.doi.org/10.1002/mgg3.981 |
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author | Cerón‐Rodríguez, Magdalena Ramón‐García, Guillermo Barajas‐Colón, Edgar Franco‐Álvarez, Isidro Salgado‐Loza, Juan L. |
author_facet | Cerón‐Rodríguez, Magdalena Ramón‐García, Guillermo Barajas‐Colón, Edgar Franco‐Álvarez, Isidro Salgado‐Loza, Juan L. |
author_sort | Cerón‐Rodríguez, Magdalena |
collection | PubMed |
description | BACKGROUND: Fabry disease (FD) has an extensive phenotypic expression associated with GLA gene variants. The GLA gene variant c.352C>T/p.Arg118Cys was considered with uncertain pathogenicity because of the finding of high residual alpha‐galactosidase A (α‐Gal A) enzyme activity, the absence of Mendelian segregation with an FD phenotype with many individuals remaining asymptomatic at old ages and the lack of globotriaosylceramide (Gb3) deposits in tissues. Gb3 deposits are found in kidneys before the progression to overt microalbuminuria and decreased glomerular filtration. METHODS: We describe a family with c.352C>T/p.Arg118Cys variant and pathognomonic signs of FD renal damage in masculine children. RESULTS: The proband died of end‐stage renal failure and we analyzed GLA gene in his offspring and found the variant in all daughters and five of seven grandchildren. In patients who we measure plasma and urinary Gb3, α‐Gal A enzyme activity, and plasma globotriaosylsphingosine (Lyso‐Gb3), these were normal or almost normal. A kidney biopsy was performed in two boys and one girl with normal renal function and characteristic signs of FD as enlarged and vacuolated epithelial cells, myelin figures, myelin‐like figures, lamellated structures in podocytes and endothelial cells, were found in boys. These boys received agalsidase beta 1 mg/kg IV infusion every other week to prevent further renal damage. CONCLUSION: This is the first report that shows a link between FD renal Gb3 deposits and c.352C>T/p.Arg118Cys variant, supporting pathogenicity of a variant considered until now with uncertain pathogenicity. |
format | Online Article Text |
id | pubmed-6825844 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-68258442019-11-07 Renal globotriaosylceramide deposits for Fabry disease linked to uncertain pathogenicity gene variant c.352C>T/p.Arg118Cys: A family study Cerón‐Rodríguez, Magdalena Ramón‐García, Guillermo Barajas‐Colón, Edgar Franco‐Álvarez, Isidro Salgado‐Loza, Juan L. Mol Genet Genomic Med Original Articles BACKGROUND: Fabry disease (FD) has an extensive phenotypic expression associated with GLA gene variants. The GLA gene variant c.352C>T/p.Arg118Cys was considered with uncertain pathogenicity because of the finding of high residual alpha‐galactosidase A (α‐Gal A) enzyme activity, the absence of Mendelian segregation with an FD phenotype with many individuals remaining asymptomatic at old ages and the lack of globotriaosylceramide (Gb3) deposits in tissues. Gb3 deposits are found in kidneys before the progression to overt microalbuminuria and decreased glomerular filtration. METHODS: We describe a family with c.352C>T/p.Arg118Cys variant and pathognomonic signs of FD renal damage in masculine children. RESULTS: The proband died of end‐stage renal failure and we analyzed GLA gene in his offspring and found the variant in all daughters and five of seven grandchildren. In patients who we measure plasma and urinary Gb3, α‐Gal A enzyme activity, and plasma globotriaosylsphingosine (Lyso‐Gb3), these were normal or almost normal. A kidney biopsy was performed in two boys and one girl with normal renal function and characteristic signs of FD as enlarged and vacuolated epithelial cells, myelin figures, myelin‐like figures, lamellated structures in podocytes and endothelial cells, were found in boys. These boys received agalsidase beta 1 mg/kg IV infusion every other week to prevent further renal damage. CONCLUSION: This is the first report that shows a link between FD renal Gb3 deposits and c.352C>T/p.Arg118Cys variant, supporting pathogenicity of a variant considered until now with uncertain pathogenicity. John Wiley and Sons Inc. 2019-09-30 /pmc/articles/PMC6825844/ /pubmed/31566927 http://dx.doi.org/10.1002/mgg3.981 Text en © 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Cerón‐Rodríguez, Magdalena Ramón‐García, Guillermo Barajas‐Colón, Edgar Franco‐Álvarez, Isidro Salgado‐Loza, Juan L. Renal globotriaosylceramide deposits for Fabry disease linked to uncertain pathogenicity gene variant c.352C>T/p.Arg118Cys: A family study |
title | Renal globotriaosylceramide deposits for Fabry disease linked to uncertain pathogenicity gene variant c.352C>T/p.Arg118Cys: A family study |
title_full | Renal globotriaosylceramide deposits for Fabry disease linked to uncertain pathogenicity gene variant c.352C>T/p.Arg118Cys: A family study |
title_fullStr | Renal globotriaosylceramide deposits for Fabry disease linked to uncertain pathogenicity gene variant c.352C>T/p.Arg118Cys: A family study |
title_full_unstemmed | Renal globotriaosylceramide deposits for Fabry disease linked to uncertain pathogenicity gene variant c.352C>T/p.Arg118Cys: A family study |
title_short | Renal globotriaosylceramide deposits for Fabry disease linked to uncertain pathogenicity gene variant c.352C>T/p.Arg118Cys: A family study |
title_sort | renal globotriaosylceramide deposits for fabry disease linked to uncertain pathogenicity gene variant c.352c>t/p.arg118cys: a family study |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6825844/ https://www.ncbi.nlm.nih.gov/pubmed/31566927 http://dx.doi.org/10.1002/mgg3.981 |
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