Genotype-Phenotype Correlations for Pathogenic COL4A3–COL4A5 Variants in X-Linked, Autosomal Recessive, and Autosomal Dominant Alport Syndrome

Alport syndrome is inherited as an X-linked (XL), autosomal recessive (AR), or autosomal dominant (AD) disease, where pathogenic COL4A3 – COL4A5 variants affect the basement membrane collagen IV α3α4α5 network. About 50% of pathogenic variants in each gene (major rearrangements and large deletions i...
Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Judy Savige [verfasserIn] Mary Huang [verfasserIn] Marina Shenelli Croos Dabrera [verfasserIn] Krushnam Shukla [verfasserIn] Joel Gibson [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	genotype-phenotype correlation Alport syndrome COL4A3 COL4A4 COL4A5 XL Alport syndrome

Übergeordnetes Werk:	In: Frontiers in Medicine - Frontiers Media S.A., 2014, 9(2022)
Übergeordnetes Werk:	volume:9 ; year:2022

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fmed.2022.865034

Katalog-ID:	DOAJ04073501X

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520			\|a Alport syndrome is inherited as an X-linked (XL), autosomal recessive (AR), or autosomal dominant (AD) disease, where pathogenic COL4A3 – COL4A5 variants affect the basement membrane collagen IV α3α4α5 network. About 50% of pathogenic variants in each gene (major rearrangements and large deletions in 15%, truncating variants in 20%, splicing changes in 15%) are associated with “severe” disease with earlier onset kidney failure, and hearing loss and ocular abnormalities in males with XL inheritance and in males and females with AR disease. Severe variants are also associated with early proteinuria which is itself a risk factor for kidney failure. The other half of pathogenic variants are missense changes which are mainly Gly substitutions. These are generally associated with later onset kidney failure, hearing loss, and less often with major ocular abnormalities. Further determinants of severity for missense variants for XL disease in males, and in AD disease, include Gly versus non-Gly substitutions; increased distance from a non-collagenous interruption or terminus; and Gly substitutions with a more (Arg, Glu, Asp, Val, and Trp) or less disruptive (Ala, Ser, and Cys) residue. Understanding genotype-phenotype correlations in Alport syndrome is important because they help predict the likely age at kidney failure, and the need for early and aggressive management with renin-angiotensin system blockade and other therapies. Genotype-phenotype correlations also help standardize patients with Alport syndrome undergoing trials of clinical treatment. It is unclear whether severe variants predispose more often to kidney cysts or coincidental IgA glomerulonephritis which are recognized increasingly in COL4A3-, COL4A4 - and COL4A5-associated disease.
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allfields	10.3389/fmed.2022.865034 doi (DE-627)DOAJ04073501X (DE-599)DOAJd0688c9585784e39bfcf00519e72e041 DE-627 ger DE-627 rakwb eng R5-920 Judy Savige verfasserin aut Genotype-Phenotype Correlations for Pathogenic COL4A3–COL4A5 Variants in X-Linked, Autosomal Recessive, and Autosomal Dominant Alport Syndrome 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Alport syndrome is inherited as an X-linked (XL), autosomal recessive (AR), or autosomal dominant (AD) disease, where pathogenic COL4A3 – COL4A5 variants affect the basement membrane collagen IV α3α4α5 network. About 50% of pathogenic variants in each gene (major rearrangements and large deletions in 15%, truncating variants in 20%, splicing changes in 15%) are associated with “severe” disease with earlier onset kidney failure, and hearing loss and ocular abnormalities in males with XL inheritance and in males and females with AR disease. Severe variants are also associated with early proteinuria which is itself a risk factor for kidney failure. The other half of pathogenic variants are missense changes which are mainly Gly substitutions. These are generally associated with later onset kidney failure, hearing loss, and less often with major ocular abnormalities. Further determinants of severity for missense variants for XL disease in males, and in AD disease, include Gly versus non-Gly substitutions; increased distance from a non-collagenous interruption or terminus; and Gly substitutions with a more (Arg, Glu, Asp, Val, and Trp) or less disruptive (Ala, Ser, and Cys) residue. Understanding genotype-phenotype correlations in Alport syndrome is important because they help predict the likely age at kidney failure, and the need for early and aggressive management with renin-angiotensin system blockade and other therapies. Genotype-phenotype correlations also help standardize patients with Alport syndrome undergoing trials of clinical treatment. It is unclear whether severe variants predispose more often to kidney cysts or coincidental IgA glomerulonephritis which are recognized increasingly in COL4A3-, COL4A4 - and COL4A5-associated disease. genotype-phenotype correlation Alport syndrome COL4A3 COL4A4 COL4A5 XL Alport syndrome Medicine (General) Mary Huang verfasserin aut Marina Shenelli Croos Dabrera verfasserin aut Krushnam Shukla verfasserin aut Joel Gibson verfasserin aut In Frontiers in Medicine Frontiers Media S.A., 2014 9(2022) (DE-627)789482991 (DE-600)2775999-4 2296858X nnns volume:9 year:2022 https://doi.org/10.3389/fmed.2022.865034 kostenfrei https://doaj.org/article/d0688c9585784e39bfcf00519e72e041 kostenfrei https://www.frontiersin.org/articles/10.3389/fmed.2022.865034/full kostenfrei https://doaj.org/toc/2296-858X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2022
spelling	10.3389/fmed.2022.865034 doi (DE-627)DOAJ04073501X (DE-599)DOAJd0688c9585784e39bfcf00519e72e041 DE-627 ger DE-627 rakwb eng R5-920 Judy Savige verfasserin aut Genotype-Phenotype Correlations for Pathogenic COL4A3–COL4A5 Variants in X-Linked, Autosomal Recessive, and Autosomal Dominant Alport Syndrome 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Alport syndrome is inherited as an X-linked (XL), autosomal recessive (AR), or autosomal dominant (AD) disease, where pathogenic COL4A3 – COL4A5 variants affect the basement membrane collagen IV α3α4α5 network. About 50% of pathogenic variants in each gene (major rearrangements and large deletions in 15%, truncating variants in 20%, splicing changes in 15%) are associated with “severe” disease with earlier onset kidney failure, and hearing loss and ocular abnormalities in males with XL inheritance and in males and females with AR disease. Severe variants are also associated with early proteinuria which is itself a risk factor for kidney failure. The other half of pathogenic variants are missense changes which are mainly Gly substitutions. These are generally associated with later onset kidney failure, hearing loss, and less often with major ocular abnormalities. Further determinants of severity for missense variants for XL disease in males, and in AD disease, include Gly versus non-Gly substitutions; increased distance from a non-collagenous interruption or terminus; and Gly substitutions with a more (Arg, Glu, Asp, Val, and Trp) or less disruptive (Ala, Ser, and Cys) residue. Understanding genotype-phenotype correlations in Alport syndrome is important because they help predict the likely age at kidney failure, and the need for early and aggressive management with renin-angiotensin system blockade and other therapies. Genotype-phenotype correlations also help standardize patients with Alport syndrome undergoing trials of clinical treatment. It is unclear whether severe variants predispose more often to kidney cysts or coincidental IgA glomerulonephritis which are recognized increasingly in COL4A3-, COL4A4 - and COL4A5-associated disease. genotype-phenotype correlation Alport syndrome COL4A3 COL4A4 COL4A5 XL Alport syndrome Medicine (General) Mary Huang verfasserin aut Marina Shenelli Croos Dabrera verfasserin aut Krushnam Shukla verfasserin aut Joel Gibson verfasserin aut In Frontiers in Medicine Frontiers Media S.A., 2014 9(2022) (DE-627)789482991 (DE-600)2775999-4 2296858X nnns volume:9 year:2022 https://doi.org/10.3389/fmed.2022.865034 kostenfrei https://doaj.org/article/d0688c9585784e39bfcf00519e72e041 kostenfrei https://www.frontiersin.org/articles/10.3389/fmed.2022.865034/full kostenfrei https://doaj.org/toc/2296-858X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2022
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allfieldsGer	10.3389/fmed.2022.865034 doi (DE-627)DOAJ04073501X (DE-599)DOAJd0688c9585784e39bfcf00519e72e041 DE-627 ger DE-627 rakwb eng R5-920 Judy Savige verfasserin aut Genotype-Phenotype Correlations for Pathogenic COL4A3–COL4A5 Variants in X-Linked, Autosomal Recessive, and Autosomal Dominant Alport Syndrome 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Alport syndrome is inherited as an X-linked (XL), autosomal recessive (AR), or autosomal dominant (AD) disease, where pathogenic COL4A3 – COL4A5 variants affect the basement membrane collagen IV α3α4α5 network. About 50% of pathogenic variants in each gene (major rearrangements and large deletions in 15%, truncating variants in 20%, splicing changes in 15%) are associated with “severe” disease with earlier onset kidney failure, and hearing loss and ocular abnormalities in males with XL inheritance and in males and females with AR disease. Severe variants are also associated with early proteinuria which is itself a risk factor for kidney failure. The other half of pathogenic variants are missense changes which are mainly Gly substitutions. These are generally associated with later onset kidney failure, hearing loss, and less often with major ocular abnormalities. Further determinants of severity for missense variants for XL disease in males, and in AD disease, include Gly versus non-Gly substitutions; increased distance from a non-collagenous interruption or terminus; and Gly substitutions with a more (Arg, Glu, Asp, Val, and Trp) or less disruptive (Ala, Ser, and Cys) residue. Understanding genotype-phenotype correlations in Alport syndrome is important because they help predict the likely age at kidney failure, and the need for early and aggressive management with renin-angiotensin system blockade and other therapies. Genotype-phenotype correlations also help standardize patients with Alport syndrome undergoing trials of clinical treatment. It is unclear whether severe variants predispose more often to kidney cysts or coincidental IgA glomerulonephritis which are recognized increasingly in COL4A3-, COL4A4 - and COL4A5-associated disease. genotype-phenotype correlation Alport syndrome COL4A3 COL4A4 COL4A5 XL Alport syndrome Medicine (General) Mary Huang verfasserin aut Marina Shenelli Croos Dabrera verfasserin aut Krushnam Shukla verfasserin aut Joel Gibson verfasserin aut In Frontiers in Medicine Frontiers Media S.A., 2014 9(2022) (DE-627)789482991 (DE-600)2775999-4 2296858X nnns volume:9 year:2022 https://doi.org/10.3389/fmed.2022.865034 kostenfrei https://doaj.org/article/d0688c9585784e39bfcf00519e72e041 kostenfrei https://www.frontiersin.org/articles/10.3389/fmed.2022.865034/full kostenfrei https://doaj.org/toc/2296-858X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2022
allfieldsSound	10.3389/fmed.2022.865034 doi (DE-627)DOAJ04073501X (DE-599)DOAJd0688c9585784e39bfcf00519e72e041 DE-627 ger DE-627 rakwb eng R5-920 Judy Savige verfasserin aut Genotype-Phenotype Correlations for Pathogenic COL4A3–COL4A5 Variants in X-Linked, Autosomal Recessive, and Autosomal Dominant Alport Syndrome 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Alport syndrome is inherited as an X-linked (XL), autosomal recessive (AR), or autosomal dominant (AD) disease, where pathogenic COL4A3 – COL4A5 variants affect the basement membrane collagen IV α3α4α5 network. About 50% of pathogenic variants in each gene (major rearrangements and large deletions in 15%, truncating variants in 20%, splicing changes in 15%) are associated with “severe” disease with earlier onset kidney failure, and hearing loss and ocular abnormalities in males with XL inheritance and in males and females with AR disease. Severe variants are also associated with early proteinuria which is itself a risk factor for kidney failure. The other half of pathogenic variants are missense changes which are mainly Gly substitutions. These are generally associated with later onset kidney failure, hearing loss, and less often with major ocular abnormalities. Further determinants of severity for missense variants for XL disease in males, and in AD disease, include Gly versus non-Gly substitutions; increased distance from a non-collagenous interruption or terminus; and Gly substitutions with a more (Arg, Glu, Asp, Val, and Trp) or less disruptive (Ala, Ser, and Cys) residue. Understanding genotype-phenotype correlations in Alport syndrome is important because they help predict the likely age at kidney failure, and the need for early and aggressive management with renin-angiotensin system blockade and other therapies. Genotype-phenotype correlations also help standardize patients with Alport syndrome undergoing trials of clinical treatment. It is unclear whether severe variants predispose more often to kidney cysts or coincidental IgA glomerulonephritis which are recognized increasingly in COL4A3-, COL4A4 - and COL4A5-associated disease. genotype-phenotype correlation Alport syndrome COL4A3 COL4A4 COL4A5 XL Alport syndrome Medicine (General) Mary Huang verfasserin aut Marina Shenelli Croos Dabrera verfasserin aut Krushnam Shukla verfasserin aut Joel Gibson verfasserin aut In Frontiers in Medicine Frontiers Media S.A., 2014 9(2022) (DE-627)789482991 (DE-600)2775999-4 2296858X nnns volume:9 year:2022 https://doi.org/10.3389/fmed.2022.865034 kostenfrei https://doaj.org/article/d0688c9585784e39bfcf00519e72e041 kostenfrei https://www.frontiersin.org/articles/10.3389/fmed.2022.865034/full kostenfrei https://doaj.org/toc/2296-858X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2022
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authorswithroles_txt_mv	Judy Savige @@aut@@ Mary Huang @@aut@@ Marina Shenelli Croos Dabrera @@aut@@ Krushnam Shukla @@aut@@ Joel Gibson @@aut@@
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callnumber-first	R - Medicine
author	Judy Savige
spellingShingle	Judy Savige misc R5-920 misc genotype-phenotype correlation misc Alport syndrome misc COL4A3 misc COL4A4 misc COL4A5 misc XL Alport syndrome misc Medicine (General) Genotype-Phenotype Correlations for Pathogenic COL4A3–COL4A5 Variants in X-Linked, Autosomal Recessive, and Autosomal Dominant Alport Syndrome
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topic_title	R5-920 Genotype-Phenotype Correlations for Pathogenic COL4A3–COL4A5 Variants in X-Linked, Autosomal Recessive, and Autosomal Dominant Alport Syndrome genotype-phenotype correlation Alport syndrome COL4A3 COL4A4 COL4A5 XL Alport syndrome
topic	misc R5-920 misc genotype-phenotype correlation misc Alport syndrome misc COL4A3 misc COL4A4 misc COL4A5 misc XL Alport syndrome misc Medicine (General)
topic_unstemmed	misc R5-920 misc genotype-phenotype correlation misc Alport syndrome misc COL4A3 misc COL4A4 misc COL4A5 misc XL Alport syndrome misc Medicine (General)
topic_browse	misc R5-920 misc genotype-phenotype correlation misc Alport syndrome misc COL4A3 misc COL4A4 misc COL4A5 misc XL Alport syndrome misc Medicine (General)
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title	Genotype-Phenotype Correlations for Pathogenic COL4A3–COL4A5 Variants in X-Linked, Autosomal Recessive, and Autosomal Dominant Alport Syndrome
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title_full	Genotype-Phenotype Correlations for Pathogenic COL4A3–COL4A5 Variants in X-Linked, Autosomal Recessive, and Autosomal Dominant Alport Syndrome
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title_sort	genotype-phenotype correlations for pathogenic col4a3–col4a5 variants in x-linked, autosomal recessive, and autosomal dominant alport syndrome
callnumber	R5-920
title_auth	Genotype-Phenotype Correlations for Pathogenic COL4A3–COL4A5 Variants in X-Linked, Autosomal Recessive, and Autosomal Dominant Alport Syndrome
abstract	Alport syndrome is inherited as an X-linked (XL), autosomal recessive (AR), or autosomal dominant (AD) disease, where pathogenic COL4A3 – COL4A5 variants affect the basement membrane collagen IV α3α4α5 network. About 50% of pathogenic variants in each gene (major rearrangements and large deletions in 15%, truncating variants in 20%, splicing changes in 15%) are associated with “severe” disease with earlier onset kidney failure, and hearing loss and ocular abnormalities in males with XL inheritance and in males and females with AR disease. Severe variants are also associated with early proteinuria which is itself a risk factor for kidney failure. The other half of pathogenic variants are missense changes which are mainly Gly substitutions. These are generally associated with later onset kidney failure, hearing loss, and less often with major ocular abnormalities. Further determinants of severity for missense variants for XL disease in males, and in AD disease, include Gly versus non-Gly substitutions; increased distance from a non-collagenous interruption or terminus; and Gly substitutions with a more (Arg, Glu, Asp, Val, and Trp) or less disruptive (Ala, Ser, and Cys) residue. Understanding genotype-phenotype correlations in Alport syndrome is important because they help predict the likely age at kidney failure, and the need for early and aggressive management with renin-angiotensin system blockade and other therapies. Genotype-phenotype correlations also help standardize patients with Alport syndrome undergoing trials of clinical treatment. It is unclear whether severe variants predispose more often to kidney cysts or coincidental IgA glomerulonephritis which are recognized increasingly in COL4A3-, COL4A4 - and COL4A5-associated disease.
abstractGer	Alport syndrome is inherited as an X-linked (XL), autosomal recessive (AR), or autosomal dominant (AD) disease, where pathogenic COL4A3 – COL4A5 variants affect the basement membrane collagen IV α3α4α5 network. About 50% of pathogenic variants in each gene (major rearrangements and large deletions in 15%, truncating variants in 20%, splicing changes in 15%) are associated with “severe” disease with earlier onset kidney failure, and hearing loss and ocular abnormalities in males with XL inheritance and in males and females with AR disease. Severe variants are also associated with early proteinuria which is itself a risk factor for kidney failure. The other half of pathogenic variants are missense changes which are mainly Gly substitutions. These are generally associated with later onset kidney failure, hearing loss, and less often with major ocular abnormalities. Further determinants of severity for missense variants for XL disease in males, and in AD disease, include Gly versus non-Gly substitutions; increased distance from a non-collagenous interruption or terminus; and Gly substitutions with a more (Arg, Glu, Asp, Val, and Trp) or less disruptive (Ala, Ser, and Cys) residue. Understanding genotype-phenotype correlations in Alport syndrome is important because they help predict the likely age at kidney failure, and the need for early and aggressive management with renin-angiotensin system blockade and other therapies. Genotype-phenotype correlations also help standardize patients with Alport syndrome undergoing trials of clinical treatment. It is unclear whether severe variants predispose more often to kidney cysts or coincidental IgA glomerulonephritis which are recognized increasingly in COL4A3-, COL4A4 - and COL4A5-associated disease.
abstract_unstemmed	Alport syndrome is inherited as an X-linked (XL), autosomal recessive (AR), or autosomal dominant (AD) disease, where pathogenic COL4A3 – COL4A5 variants affect the basement membrane collagen IV α3α4α5 network. About 50% of pathogenic variants in each gene (major rearrangements and large deletions in 15%, truncating variants in 20%, splicing changes in 15%) are associated with “severe” disease with earlier onset kidney failure, and hearing loss and ocular abnormalities in males with XL inheritance and in males and females with AR disease. Severe variants are also associated with early proteinuria which is itself a risk factor for kidney failure. The other half of pathogenic variants are missense changes which are mainly Gly substitutions. These are generally associated with later onset kidney failure, hearing loss, and less often with major ocular abnormalities. Further determinants of severity for missense variants for XL disease in males, and in AD disease, include Gly versus non-Gly substitutions; increased distance from a non-collagenous interruption or terminus; and Gly substitutions with a more (Arg, Glu, Asp, Val, and Trp) or less disruptive (Ala, Ser, and Cys) residue. Understanding genotype-phenotype correlations in Alport syndrome is important because they help predict the likely age at kidney failure, and the need for early and aggressive management with renin-angiotensin system blockade and other therapies. Genotype-phenotype correlations also help standardize patients with Alport syndrome undergoing trials of clinical treatment. It is unclear whether severe variants predispose more often to kidney cysts or coincidental IgA glomerulonephritis which are recognized increasingly in COL4A3-, COL4A4 - and COL4A5-associated disease.
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title_short	Genotype-Phenotype Correlations for Pathogenic COL4A3–COL4A5 Variants in X-Linked, Autosomal Recessive, and Autosomal Dominant Alport Syndrome
url	https://doi.org/10.3389/fmed.2022.865034 https://doaj.org/article/d0688c9585784e39bfcf00519e72e041 https://www.frontiersin.org/articles/10.3389/fmed.2022.865034/full https://doaj.org/toc/2296-858X
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Understanding genotype-phenotype correlations in Alport syndrome is important because they help predict the likely age at kidney failure, and the need for early and aggressive management with renin-angiotensin system blockade and other therapies. Genotype-phenotype correlations also help standardize patients with Alport syndrome undergoing trials of clinical treatment. 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Genotype-Phenotype Correlations for Pathogenic COL4A3–COL4A5 Variants in X-Linked, Autosomal Recessive, and Autosomal Dominant Alport Syndrome

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