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Case report: De novo mutation of a-galactosidase A in a female patient with end-stage renal disease: report of a case of late diagnosis of Anderson–Fabry disease
Background: Anderson–Fabry disease (AFD) is an X-linked disease that results from reduced activity of the enzyme galactosidase alpha (GLA). When the GLA gene sequence is altered by mutations that alter the normal DNA sequence, variants of the alpha-galactosidase A enzyme are produced, which may or m...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10537954/ https://www.ncbi.nlm.nih.gov/pubmed/37779915 http://dx.doi.org/10.3389/fgene.2023.1122893 |
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author | Simonetta, Irene Riolo, Renata Todaro, Federica Donadio, Vincenzo Incensi, Alex Tuttolomondo, Antonino |
author_facet | Simonetta, Irene Riolo, Renata Todaro, Federica Donadio, Vincenzo Incensi, Alex Tuttolomondo, Antonino |
author_sort | Simonetta, Irene |
collection | PubMed |
description | Background: Anderson–Fabry disease (AFD) is an X-linked disease that results from reduced activity of the enzyme galactosidase alpha (GLA). When the GLA gene sequence is altered by mutations that alter the normal DNA sequence, variants of the alpha-galactosidase A enzyme are produced, which may or may not function. These mutations are responsible for Fabry disease, and to date, over 800 different mutations of the gene have been described in patients with Anderson–Fabry disease. In this case, we report the case of a woman who is the sole family member with this type of mutation. Case presentation: We report a case of a 52-year-old woman with end-stage chronic kidney disease in dialysis treatment. The patient’s alpha-galactosidase activity was 6.6 nmol/ml/h in whole blood, and lyso-GB3 levels were 11.45 nmol/L (normal range < 2.3 nmol/L). Alpha-galactosidase A gene sequence analysis revealed a pathogenic variant of c.947dupT in exon 6, leading to the p. I317NfsTer16 amino acid substitution. The genetic analysis did not detect the same mutation in any of the other screened family members. Conclusion: The international Fabry disease genotype-phenotype database (dbFGP) reports a pathogenic variant c.947dupT in exon 6 that is probably associated with a classical phenotype of Fabry disease. In this case report, we report the case of a woman who is the sole family member with this type of pathogenic variant. Similar situations have not been described in the literature for this pathogenic variant, and it represents an important case of inter- and intrafamilial variability in patients with Fabry disease. The literature shows that de novo pathogenic variants are frequently found in the context of Fabry disease. |
format | Online Article Text |
id | pubmed-10537954 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-105379542023-09-29 Case report: De novo mutation of a-galactosidase A in a female patient with end-stage renal disease: report of a case of late diagnosis of Anderson–Fabry disease Simonetta, Irene Riolo, Renata Todaro, Federica Donadio, Vincenzo Incensi, Alex Tuttolomondo, Antonino Front Genet Genetics Background: Anderson–Fabry disease (AFD) is an X-linked disease that results from reduced activity of the enzyme galactosidase alpha (GLA). When the GLA gene sequence is altered by mutations that alter the normal DNA sequence, variants of the alpha-galactosidase A enzyme are produced, which may or may not function. These mutations are responsible for Fabry disease, and to date, over 800 different mutations of the gene have been described in patients with Anderson–Fabry disease. In this case, we report the case of a woman who is the sole family member with this type of mutation. Case presentation: We report a case of a 52-year-old woman with end-stage chronic kidney disease in dialysis treatment. The patient’s alpha-galactosidase activity was 6.6 nmol/ml/h in whole blood, and lyso-GB3 levels were 11.45 nmol/L (normal range < 2.3 nmol/L). Alpha-galactosidase A gene sequence analysis revealed a pathogenic variant of c.947dupT in exon 6, leading to the p. I317NfsTer16 amino acid substitution. The genetic analysis did not detect the same mutation in any of the other screened family members. Conclusion: The international Fabry disease genotype-phenotype database (dbFGP) reports a pathogenic variant c.947dupT in exon 6 that is probably associated with a classical phenotype of Fabry disease. In this case report, we report the case of a woman who is the sole family member with this type of pathogenic variant. Similar situations have not been described in the literature for this pathogenic variant, and it represents an important case of inter- and intrafamilial variability in patients with Fabry disease. The literature shows that de novo pathogenic variants are frequently found in the context of Fabry disease. Frontiers Media S.A. 2023-09-14 /pmc/articles/PMC10537954/ /pubmed/37779915 http://dx.doi.org/10.3389/fgene.2023.1122893 Text en Copyright © 2023 Simonetta, Riolo, Todaro, Donadio, Incensi and Tuttolomondo. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics Simonetta, Irene Riolo, Renata Todaro, Federica Donadio, Vincenzo Incensi, Alex Tuttolomondo, Antonino Case report: De novo mutation of a-galactosidase A in a female patient with end-stage renal disease: report of a case of late diagnosis of Anderson–Fabry disease |
title | Case report: De novo mutation of a-galactosidase A in a female patient with end-stage renal disease: report of a case of late diagnosis of Anderson–Fabry disease |
title_full | Case report: De novo mutation of a-galactosidase A in a female patient with end-stage renal disease: report of a case of late diagnosis of Anderson–Fabry disease |
title_fullStr | Case report: De novo mutation of a-galactosidase A in a female patient with end-stage renal disease: report of a case of late diagnosis of Anderson–Fabry disease |
title_full_unstemmed | Case report: De novo mutation of a-galactosidase A in a female patient with end-stage renal disease: report of a case of late diagnosis of Anderson–Fabry disease |
title_short | Case report: De novo mutation of a-galactosidase A in a female patient with end-stage renal disease: report of a case of late diagnosis of Anderson–Fabry disease |
title_sort | case report: de novo mutation of a-galactosidase a in a female patient with end-stage renal disease: report of a case of late diagnosis of anderson–fabry disease |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10537954/ https://www.ncbi.nlm.nih.gov/pubmed/37779915 http://dx.doi.org/10.3389/fgene.2023.1122893 |
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