New Insights into Renal Failure in a Cohort of 317 Patients with Autosomal Dominant Forms of Alport Syndrome: Report of Two Novel Heterozygous Mutations in COL4A3

Alport syndrome (AS) is a clinically and genetically heterogeneous disorder with a wide phenotypic spectrum, onset, and progression. X-linked AS (XLAS) and autosomal recessive AS (ARAS) are severe conditions, whereas the severity of autosomal dominant AS (ADAS) may vary from benign familial hematuri...

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Autores: García-Aznar, José María, Higuera, Luis de la, Besada Cerecedo, Lara, Gandiaga, Nerea Paz, Vega, Ana Isabel, Fernández Fresnedo, Gema, González-Lamuño Leguina, Domingo
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Universidad de Cantabria (UC)
Repositorio:UCrea Repositorio Abierto de la Universidad de Cantabria
Idioma:inglés
OAI Identifier:oai:repositorio.unican.es:10902/26820
Acceso en línea:https://hdl.handle.net/10902/26820
Access Level:acceso abierto
Palabra clave:Alport syndrome
COL4A3
COL4A4
ESKD
Autosomal dominant inheritance
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spelling New Insights into Renal Failure in a Cohort of 317 Patients with Autosomal Dominant Forms of Alport Syndrome: Report of Two Novel Heterozygous Mutations in COL4A3García-Aznar, José MaríaHiguera, Luis de laBesada Cerecedo, LaraGandiaga, Nerea PazVega, Ana IsabelFernández Fresnedo, GemaGonzález-Lamuño Leguina, DomingoAlport syndromeCOL4A3COL4A4ESKDAutosomal dominant inheritanceAlport syndrome (AS) is a clinically and genetically heterogeneous disorder with a wide phenotypic spectrum, onset, and progression. X-linked AS (XLAS) and autosomal recessive AS (ARAS) are severe conditions, whereas the severity of autosomal dominant AS (ADAS) may vary from benign familial hematuria to progressive renal disease with extra-renal manifestations. In this study, we collated information from the literature and analyzed a cohort of 317 patients with ADAS carrying heterozygous disease-causing mutations in COL4A3/4 including four patients from two unrelated families who carried two novel variants in COL4A3. Regarding the age of onset of the disease, 80% of patients presented urinalysis alterations (microhematuria, hematuria, and/or proteinuria) before the age of 40 years. The cumulative probability of suffering adverse renal events was mainly observed between 30 and 70 years, without statistical differences between COL4A3 and COL4A4. We observed statistically significant differences between the sexes in the age of developing ESKD in cases affected by mutations in COL4A3/4 (p value = 0.0097), suggesting that males begin experiencing earlier deterioration of renal function than women. This study supports the importance of follow-up in young patients who harbor pathogenic mutations in COL4A3/4. We update the knowledge of ADAS, highlighting differences in the progression of the disease between males and females.Funding: This research received no external funding. Acknowledgments: We kindly thank the patients and their families for agreeing to be part of this studyMDPIUniversidad de Cantabria20222022-08-19journal articlehttp://purl.org/coar/resource_type/c_6501NAhttp://purl.org/coar/version/c_be7fb7dd8ff6fe43info:eu-repo/semantics/articlehttps://hdl.handle.net/10902/26820Journal of clinical medicine 2022, 11, 4883reponame:UCrea Repositorio Abierto de la Universidad de Cantabriainstname:Universidad de Cantabria (UC)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositorio.unican.es:10902/268202026-06-02T12:39:31Z
dc.title.none.fl_str_mv New Insights into Renal Failure in a Cohort of 317 Patients with Autosomal Dominant Forms of Alport Syndrome: Report of Two Novel Heterozygous Mutations in COL4A3
title New Insights into Renal Failure in a Cohort of 317 Patients with Autosomal Dominant Forms of Alport Syndrome: Report of Two Novel Heterozygous Mutations in COL4A3
spellingShingle New Insights into Renal Failure in a Cohort of 317 Patients with Autosomal Dominant Forms of Alport Syndrome: Report of Two Novel Heterozygous Mutations in COL4A3
García-Aznar, José María
Alport syndrome
COL4A3
COL4A4
ESKD
Autosomal dominant inheritance
title_short New Insights into Renal Failure in a Cohort of 317 Patients with Autosomal Dominant Forms of Alport Syndrome: Report of Two Novel Heterozygous Mutations in COL4A3
title_full New Insights into Renal Failure in a Cohort of 317 Patients with Autosomal Dominant Forms of Alport Syndrome: Report of Two Novel Heterozygous Mutations in COL4A3
title_fullStr New Insights into Renal Failure in a Cohort of 317 Patients with Autosomal Dominant Forms of Alport Syndrome: Report of Two Novel Heterozygous Mutations in COL4A3
title_full_unstemmed New Insights into Renal Failure in a Cohort of 317 Patients with Autosomal Dominant Forms of Alport Syndrome: Report of Two Novel Heterozygous Mutations in COL4A3
title_sort New Insights into Renal Failure in a Cohort of 317 Patients with Autosomal Dominant Forms of Alport Syndrome: Report of Two Novel Heterozygous Mutations in COL4A3
dc.creator.none.fl_str_mv García-Aznar, José María
Higuera, Luis de la
Besada Cerecedo, Lara
Gandiaga, Nerea Paz
Vega, Ana Isabel
Fernández Fresnedo, Gema
González-Lamuño Leguina, Domingo
author García-Aznar, José María
author_facet García-Aznar, José María
Higuera, Luis de la
Besada Cerecedo, Lara
Gandiaga, Nerea Paz
Vega, Ana Isabel
Fernández Fresnedo, Gema
González-Lamuño Leguina, Domingo
author_role author
author2 Higuera, Luis de la
Besada Cerecedo, Lara
Gandiaga, Nerea Paz
Vega, Ana Isabel
Fernández Fresnedo, Gema
González-Lamuño Leguina, Domingo
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad de Cantabria
dc.subject.none.fl_str_mv Alport syndrome
COL4A3
COL4A4
ESKD
Autosomal dominant inheritance
topic Alport syndrome
COL4A3
COL4A4
ESKD
Autosomal dominant inheritance
description Alport syndrome (AS) is a clinically and genetically heterogeneous disorder with a wide phenotypic spectrum, onset, and progression. X-linked AS (XLAS) and autosomal recessive AS (ARAS) are severe conditions, whereas the severity of autosomal dominant AS (ADAS) may vary from benign familial hematuria to progressive renal disease with extra-renal manifestations. In this study, we collated information from the literature and analyzed a cohort of 317 patients with ADAS carrying heterozygous disease-causing mutations in COL4A3/4 including four patients from two unrelated families who carried two novel variants in COL4A3. Regarding the age of onset of the disease, 80% of patients presented urinalysis alterations (microhematuria, hematuria, and/or proteinuria) before the age of 40 years. The cumulative probability of suffering adverse renal events was mainly observed between 30 and 70 years, without statistical differences between COL4A3 and COL4A4. We observed statistically significant differences between the sexes in the age of developing ESKD in cases affected by mutations in COL4A3/4 (p value = 0.0097), suggesting that males begin experiencing earlier deterioration of renal function than women. This study supports the importance of follow-up in young patients who harbor pathogenic mutations in COL4A3/4. We update the knowledge of ADAS, highlighting differences in the progression of the disease between males and females.
publishDate 2022
dc.date.none.fl_str_mv 2022
2022-08-19
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
NA
http://purl.org/coar/version/c_be7fb7dd8ff6fe43
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/10902/26820
url https://hdl.handle.net/10902/26820
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv Journal of clinical medicine 2022, 11, 4883
reponame:UCrea Repositorio Abierto de la Universidad de Cantabria
instname:Universidad de Cantabria (UC)
instname_str Universidad de Cantabria (UC)
reponame_str UCrea Repositorio Abierto de la Universidad de Cantabria
collection UCrea Repositorio Abierto de la Universidad de Cantabria
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.300719

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