Novel Digenic Variants in COL4A4 and COL4A5 Causing X-Linked Alport Syndrome: A Case Report

Introduction: Alport syndrome (AS) is a hereditary, progressive kidney disease characterized by structural abnormalities and dysfunction of the glomerular basement membrane (GBM). AS is classified as X-linked, autosomal, and digenic. The number of cases of digenic AS has increased, but the genotype-...
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Autor*in:	Hideki Uedono [verfasserIn] Katsuhito Mori [verfasserIn] Shinya Nakatani [verfasserIn] Kohei Watanabe [verfasserIn] Rino Nakaya [verfasserIn] Fumiyuki Morioka [verfasserIn] Kazuma Sone [verfasserIn] Chie Ono [verfasserIn] Junko Hotta [verfasserIn] Akihiro Tsuda [verfasserIn] Naoya Morisada [verfasserIn] Toshiyuki Seto [verfasserIn] Kandai Nozu [verfasserIn] Masanori Emoto [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2024

Schlagwörter:	alport syndrome novel variants digenic alport syndrome

Übergeordnetes Werk:	In: Case Reports in Nephrology and Dialysis - Karger Publishers, 2016, 14(2024), 1, Seite 9
Übergeordnetes Werk:	volume:14 ; year:2024 ; number:1 ; pages:9

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1159/000535493

Katalog-ID:	DOAJ096022655

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520			\|a Introduction: Alport syndrome (AS) is a hereditary, progressive kidney disease characterized by structural abnormalities and dysfunction of the glomerular basement membrane (GBM). AS is classified as X-linked, autosomal, and digenic. The number of cases of digenic AS has increased, but the genotype-phenotype correlation of patient with digenic AS is still unclear. Here, we present a case of digenic AS with novel digenic missense variants in COL4A4 (c.827G>C, p.Gly276Ala) and COL4A5 (c.4369G>C, p.Gly1457Arg). Case Presentation: The patient was a 29-year-old Japanese man suffering from persistent microscopic hematuria and proteinuria without kidney function impairment. Kidney biopsy showed focal interstitial foam cell infiltration, global and segmental glomerulosclerosis. Immunofluorescence staining for collagen IV α5 was almost negative in the GBM and Bowman’s capsule. Electron microscopy revealed irregular thickening with lamellation and segmental thinning of the GBM. Clinical and pathological findings were consistent with AS. Comprehensive next-generation sequencing revealed a heterozygous missense variant in COL4A4 (c.827G>C, p.Gly276Ala) in exon 1 and a hemizygous missense variant in COL4A5 (c.4369G>C, p.Gly1457Arg) in exon 49 on the patient’s paternal and maternal alleles, respectively. The same digenic variants were detected in his sister, and she also showed a similar phenotype. After treatment with angiotensin-converting enzyme inhibitors, proteinuria decreased from 2.3 to 1.1 g/g creatinine, but occult blood persisted. During follow-up, kidney function has been preserved. Conclusion: The novel genotype of our case provides more information on the genotype-phenotype correlation of digenic XLAS, although long-term follow-up is required. The findings in the present case also indicate the importance of genetic tests for family members of a patient diagnosed with digenic AS.
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allfields	10.1159/000535493 doi (DE-627)DOAJ096022655 (DE-599)DOAJf5a7078a2df046aa9981ea1649ec053c DE-627 ger DE-627 rakwb eng RC870-923 Hideki Uedono verfasserin aut Novel Digenic Variants in COL4A4 and COL4A5 Causing X-Linked Alport Syndrome: A Case Report 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Introduction: Alport syndrome (AS) is a hereditary, progressive kidney disease characterized by structural abnormalities and dysfunction of the glomerular basement membrane (GBM). AS is classified as X-linked, autosomal, and digenic. The number of cases of digenic AS has increased, but the genotype-phenotype correlation of patient with digenic AS is still unclear. Here, we present a case of digenic AS with novel digenic missense variants in COL4A4 (c.827G>C, p.Gly276Ala) and COL4A5 (c.4369G>C, p.Gly1457Arg). Case Presentation: The patient was a 29-year-old Japanese man suffering from persistent microscopic hematuria and proteinuria without kidney function impairment. Kidney biopsy showed focal interstitial foam cell infiltration, global and segmental glomerulosclerosis. Immunofluorescence staining for collagen IV α5 was almost negative in the GBM and Bowman’s capsule. Electron microscopy revealed irregular thickening with lamellation and segmental thinning of the GBM. Clinical and pathological findings were consistent with AS. Comprehensive next-generation sequencing revealed a heterozygous missense variant in COL4A4 (c.827G>C, p.Gly276Ala) in exon 1 and a hemizygous missense variant in COL4A5 (c.4369G>C, p.Gly1457Arg) in exon 49 on the patient’s paternal and maternal alleles, respectively. The same digenic variants were detected in his sister, and she also showed a similar phenotype. After treatment with angiotensin-converting enzyme inhibitors, proteinuria decreased from 2.3 to 1.1 g/g creatinine, but occult blood persisted. During follow-up, kidney function has been preserved. Conclusion: The novel genotype of our case provides more information on the genotype-phenotype correlation of digenic XLAS, although long-term follow-up is required. The findings in the present case also indicate the importance of genetic tests for family members of a patient diagnosed with digenic AS. alport syndrome novel variants digenic alport syndrome Diseases of the genitourinary system. Urology Katsuhito Mori verfasserin aut Shinya Nakatani verfasserin aut Kohei Watanabe verfasserin aut Rino Nakaya verfasserin aut Fumiyuki Morioka verfasserin aut Kazuma Sone verfasserin aut Chie Ono verfasserin aut Junko Hotta verfasserin aut Akihiro Tsuda verfasserin aut Naoya Morisada verfasserin aut Toshiyuki Seto verfasserin aut Kandai Nozu verfasserin aut Masanori Emoto verfasserin aut In Case Reports in Nephrology and Dialysis Karger Publishers, 2016 14(2024), 1, Seite 9 (DE-627)818042141 (DE-600)2809879-1 22969705 nnns volume:14 year:2024 number:1 pages:9 https://doi.org/10.1159/000535493 kostenfrei https://doaj.org/article/f5a7078a2df046aa9981ea1649ec053c kostenfrei https://beta.karger.com/Article/FullText/535493 kostenfrei https://doaj.org/toc/2296-9705 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2018 GBV_ILN_2055 GBV_ILN_2111 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 14 2024 1 9
spelling	10.1159/000535493 doi (DE-627)DOAJ096022655 (DE-599)DOAJf5a7078a2df046aa9981ea1649ec053c DE-627 ger DE-627 rakwb eng RC870-923 Hideki Uedono verfasserin aut Novel Digenic Variants in COL4A4 and COL4A5 Causing X-Linked Alport Syndrome: A Case Report 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Introduction: Alport syndrome (AS) is a hereditary, progressive kidney disease characterized by structural abnormalities and dysfunction of the glomerular basement membrane (GBM). AS is classified as X-linked, autosomal, and digenic. The number of cases of digenic AS has increased, but the genotype-phenotype correlation of patient with digenic AS is still unclear. Here, we present a case of digenic AS with novel digenic missense variants in COL4A4 (c.827G>C, p.Gly276Ala) and COL4A5 (c.4369G>C, p.Gly1457Arg). Case Presentation: The patient was a 29-year-old Japanese man suffering from persistent microscopic hematuria and proteinuria without kidney function impairment. Kidney biopsy showed focal interstitial foam cell infiltration, global and segmental glomerulosclerosis. Immunofluorescence staining for collagen IV α5 was almost negative in the GBM and Bowman’s capsule. Electron microscopy revealed irregular thickening with lamellation and segmental thinning of the GBM. Clinical and pathological findings were consistent with AS. Comprehensive next-generation sequencing revealed a heterozygous missense variant in COL4A4 (c.827G>C, p.Gly276Ala) in exon 1 and a hemizygous missense variant in COL4A5 (c.4369G>C, p.Gly1457Arg) in exon 49 on the patient’s paternal and maternal alleles, respectively. The same digenic variants were detected in his sister, and she also showed a similar phenotype. After treatment with angiotensin-converting enzyme inhibitors, proteinuria decreased from 2.3 to 1.1 g/g creatinine, but occult blood persisted. During follow-up, kidney function has been preserved. Conclusion: The novel genotype of our case provides more information on the genotype-phenotype correlation of digenic XLAS, although long-term follow-up is required. The findings in the present case also indicate the importance of genetic tests for family members of a patient diagnosed with digenic AS. alport syndrome novel variants digenic alport syndrome Diseases of the genitourinary system. Urology Katsuhito Mori verfasserin aut Shinya Nakatani verfasserin aut Kohei Watanabe verfasserin aut Rino Nakaya verfasserin aut Fumiyuki Morioka verfasserin aut Kazuma Sone verfasserin aut Chie Ono verfasserin aut Junko Hotta verfasserin aut Akihiro Tsuda verfasserin aut Naoya Morisada verfasserin aut Toshiyuki Seto verfasserin aut Kandai Nozu verfasserin aut Masanori Emoto verfasserin aut In Case Reports in Nephrology and Dialysis Karger Publishers, 2016 14(2024), 1, Seite 9 (DE-627)818042141 (DE-600)2809879-1 22969705 nnns volume:14 year:2024 number:1 pages:9 https://doi.org/10.1159/000535493 kostenfrei https://doaj.org/article/f5a7078a2df046aa9981ea1649ec053c kostenfrei https://beta.karger.com/Article/FullText/535493 kostenfrei https://doaj.org/toc/2296-9705 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2018 GBV_ILN_2055 GBV_ILN_2111 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 14 2024 1 9
allfields_unstemmed	10.1159/000535493 doi (DE-627)DOAJ096022655 (DE-599)DOAJf5a7078a2df046aa9981ea1649ec053c DE-627 ger DE-627 rakwb eng RC870-923 Hideki Uedono verfasserin aut Novel Digenic Variants in COL4A4 and COL4A5 Causing X-Linked Alport Syndrome: A Case Report 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Introduction: Alport syndrome (AS) is a hereditary, progressive kidney disease characterized by structural abnormalities and dysfunction of the glomerular basement membrane (GBM). AS is classified as X-linked, autosomal, and digenic. The number of cases of digenic AS has increased, but the genotype-phenotype correlation of patient with digenic AS is still unclear. Here, we present a case of digenic AS with novel digenic missense variants in COL4A4 (c.827G>C, p.Gly276Ala) and COL4A5 (c.4369G>C, p.Gly1457Arg). Case Presentation: The patient was a 29-year-old Japanese man suffering from persistent microscopic hematuria and proteinuria without kidney function impairment. Kidney biopsy showed focal interstitial foam cell infiltration, global and segmental glomerulosclerosis. Immunofluorescence staining for collagen IV α5 was almost negative in the GBM and Bowman’s capsule. Electron microscopy revealed irregular thickening with lamellation and segmental thinning of the GBM. Clinical and pathological findings were consistent with AS. Comprehensive next-generation sequencing revealed a heterozygous missense variant in COL4A4 (c.827G>C, p.Gly276Ala) in exon 1 and a hemizygous missense variant in COL4A5 (c.4369G>C, p.Gly1457Arg) in exon 49 on the patient’s paternal and maternal alleles, respectively. The same digenic variants were detected in his sister, and she also showed a similar phenotype. After treatment with angiotensin-converting enzyme inhibitors, proteinuria decreased from 2.3 to 1.1 g/g creatinine, but occult blood persisted. During follow-up, kidney function has been preserved. Conclusion: The novel genotype of our case provides more information on the genotype-phenotype correlation of digenic XLAS, although long-term follow-up is required. The findings in the present case also indicate the importance of genetic tests for family members of a patient diagnosed with digenic AS. alport syndrome novel variants digenic alport syndrome Diseases of the genitourinary system. Urology Katsuhito Mori verfasserin aut Shinya Nakatani verfasserin aut Kohei Watanabe verfasserin aut Rino Nakaya verfasserin aut Fumiyuki Morioka verfasserin aut Kazuma Sone verfasserin aut Chie Ono verfasserin aut Junko Hotta verfasserin aut Akihiro Tsuda verfasserin aut Naoya Morisada verfasserin aut Toshiyuki Seto verfasserin aut Kandai Nozu verfasserin aut Masanori Emoto verfasserin aut In Case Reports in Nephrology and Dialysis Karger Publishers, 2016 14(2024), 1, Seite 9 (DE-627)818042141 (DE-600)2809879-1 22969705 nnns volume:14 year:2024 number:1 pages:9 https://doi.org/10.1159/000535493 kostenfrei https://doaj.org/article/f5a7078a2df046aa9981ea1649ec053c kostenfrei https://beta.karger.com/Article/FullText/535493 kostenfrei https://doaj.org/toc/2296-9705 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2018 GBV_ILN_2055 GBV_ILN_2111 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 14 2024 1 9
allfieldsGer	10.1159/000535493 doi (DE-627)DOAJ096022655 (DE-599)DOAJf5a7078a2df046aa9981ea1649ec053c DE-627 ger DE-627 rakwb eng RC870-923 Hideki Uedono verfasserin aut Novel Digenic Variants in COL4A4 and COL4A5 Causing X-Linked Alport Syndrome: A Case Report 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Introduction: Alport syndrome (AS) is a hereditary, progressive kidney disease characterized by structural abnormalities and dysfunction of the glomerular basement membrane (GBM). AS is classified as X-linked, autosomal, and digenic. The number of cases of digenic AS has increased, but the genotype-phenotype correlation of patient with digenic AS is still unclear. Here, we present a case of digenic AS with novel digenic missense variants in COL4A4 (c.827G>C, p.Gly276Ala) and COL4A5 (c.4369G>C, p.Gly1457Arg). Case Presentation: The patient was a 29-year-old Japanese man suffering from persistent microscopic hematuria and proteinuria without kidney function impairment. Kidney biopsy showed focal interstitial foam cell infiltration, global and segmental glomerulosclerosis. Immunofluorescence staining for collagen IV α5 was almost negative in the GBM and Bowman’s capsule. Electron microscopy revealed irregular thickening with lamellation and segmental thinning of the GBM. Clinical and pathological findings were consistent with AS. Comprehensive next-generation sequencing revealed a heterozygous missense variant in COL4A4 (c.827G>C, p.Gly276Ala) in exon 1 and a hemizygous missense variant in COL4A5 (c.4369G>C, p.Gly1457Arg) in exon 49 on the patient’s paternal and maternal alleles, respectively. The same digenic variants were detected in his sister, and she also showed a similar phenotype. After treatment with angiotensin-converting enzyme inhibitors, proteinuria decreased from 2.3 to 1.1 g/g creatinine, but occult blood persisted. During follow-up, kidney function has been preserved. Conclusion: The novel genotype of our case provides more information on the genotype-phenotype correlation of digenic XLAS, although long-term follow-up is required. The findings in the present case also indicate the importance of genetic tests for family members of a patient diagnosed with digenic AS. alport syndrome novel variants digenic alport syndrome Diseases of the genitourinary system. Urology Katsuhito Mori verfasserin aut Shinya Nakatani verfasserin aut Kohei Watanabe verfasserin aut Rino Nakaya verfasserin aut Fumiyuki Morioka verfasserin aut Kazuma Sone verfasserin aut Chie Ono verfasserin aut Junko Hotta verfasserin aut Akihiro Tsuda verfasserin aut Naoya Morisada verfasserin aut Toshiyuki Seto verfasserin aut Kandai Nozu verfasserin aut Masanori Emoto verfasserin aut In Case Reports in Nephrology and Dialysis Karger Publishers, 2016 14(2024), 1, Seite 9 (DE-627)818042141 (DE-600)2809879-1 22969705 nnns volume:14 year:2024 number:1 pages:9 https://doi.org/10.1159/000535493 kostenfrei https://doaj.org/article/f5a7078a2df046aa9981ea1649ec053c kostenfrei https://beta.karger.com/Article/FullText/535493 kostenfrei https://doaj.org/toc/2296-9705 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2018 GBV_ILN_2055 GBV_ILN_2111 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 14 2024 1 9
allfieldsSound	10.1159/000535493 doi (DE-627)DOAJ096022655 (DE-599)DOAJf5a7078a2df046aa9981ea1649ec053c DE-627 ger DE-627 rakwb eng RC870-923 Hideki Uedono verfasserin aut Novel Digenic Variants in COL4A4 and COL4A5 Causing X-Linked Alport Syndrome: A Case Report 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Introduction: Alport syndrome (AS) is a hereditary, progressive kidney disease characterized by structural abnormalities and dysfunction of the glomerular basement membrane (GBM). AS is classified as X-linked, autosomal, and digenic. The number of cases of digenic AS has increased, but the genotype-phenotype correlation of patient with digenic AS is still unclear. Here, we present a case of digenic AS with novel digenic missense variants in COL4A4 (c.827G>C, p.Gly276Ala) and COL4A5 (c.4369G>C, p.Gly1457Arg). Case Presentation: The patient was a 29-year-old Japanese man suffering from persistent microscopic hematuria and proteinuria without kidney function impairment. Kidney biopsy showed focal interstitial foam cell infiltration, global and segmental glomerulosclerosis. Immunofluorescence staining for collagen IV α5 was almost negative in the GBM and Bowman’s capsule. Electron microscopy revealed irregular thickening with lamellation and segmental thinning of the GBM. Clinical and pathological findings were consistent with AS. Comprehensive next-generation sequencing revealed a heterozygous missense variant in COL4A4 (c.827G>C, p.Gly276Ala) in exon 1 and a hemizygous missense variant in COL4A5 (c.4369G>C, p.Gly1457Arg) in exon 49 on the patient’s paternal and maternal alleles, respectively. The same digenic variants were detected in his sister, and she also showed a similar phenotype. After treatment with angiotensin-converting enzyme inhibitors, proteinuria decreased from 2.3 to 1.1 g/g creatinine, but occult blood persisted. During follow-up, kidney function has been preserved. Conclusion: The novel genotype of our case provides more information on the genotype-phenotype correlation of digenic XLAS, although long-term follow-up is required. The findings in the present case also indicate the importance of genetic tests for family members of a patient diagnosed with digenic AS. alport syndrome novel variants digenic alport syndrome Diseases of the genitourinary system. Urology Katsuhito Mori verfasserin aut Shinya Nakatani verfasserin aut Kohei Watanabe verfasserin aut Rino Nakaya verfasserin aut Fumiyuki Morioka verfasserin aut Kazuma Sone verfasserin aut Chie Ono verfasserin aut Junko Hotta verfasserin aut Akihiro Tsuda verfasserin aut Naoya Morisada verfasserin aut Toshiyuki Seto verfasserin aut Kandai Nozu verfasserin aut Masanori Emoto verfasserin aut In Case Reports in Nephrology and Dialysis Karger Publishers, 2016 14(2024), 1, Seite 9 (DE-627)818042141 (DE-600)2809879-1 22969705 nnns volume:14 year:2024 number:1 pages:9 https://doi.org/10.1159/000535493 kostenfrei https://doaj.org/article/f5a7078a2df046aa9981ea1649ec053c kostenfrei https://beta.karger.com/Article/FullText/535493 kostenfrei https://doaj.org/toc/2296-9705 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2018 GBV_ILN_2055 GBV_ILN_2111 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 14 2024 1 9
language	English
source	In Case Reports in Nephrology and Dialysis 14(2024), 1, Seite 9 volume:14 year:2024 number:1 pages:9
sourceStr	In Case Reports in Nephrology and Dialysis 14(2024), 1, Seite 9 volume:14 year:2024 number:1 pages:9
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	alport syndrome novel variants digenic alport syndrome Diseases of the genitourinary system. Urology
isfreeaccess_bool	true
container_title	Case Reports in Nephrology and Dialysis
authorswithroles_txt_mv	Hideki Uedono @@aut@@ Katsuhito Mori @@aut@@ Shinya Nakatani @@aut@@ Kohei Watanabe @@aut@@ Rino Nakaya @@aut@@ Fumiyuki Morioka @@aut@@ Kazuma Sone @@aut@@ Chie Ono @@aut@@ Junko Hotta @@aut@@ Akihiro Tsuda @@aut@@ Naoya Morisada @@aut@@ Toshiyuki Seto @@aut@@ Kandai Nozu @@aut@@ Masanori Emoto @@aut@@
publishDateDaySort_date	2024-01-01T00:00:00Z
hierarchy_top_id	818042141
id	DOAJ096022655
language_de	englisch
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callnumber-first	R - Medicine
author	Hideki Uedono
spellingShingle	Hideki Uedono misc RC870-923 misc alport syndrome misc novel variants misc digenic alport syndrome misc Diseases of the genitourinary system. Urology Novel Digenic Variants in COL4A4 and COL4A5 Causing X-Linked Alport Syndrome: A Case Report
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topic_title	RC870-923 Novel Digenic Variants in COL4A4 and COL4A5 Causing X-Linked Alport Syndrome: A Case Report alport syndrome novel variants digenic alport syndrome
topic	misc RC870-923 misc alport syndrome misc novel variants misc digenic alport syndrome misc Diseases of the genitourinary system. Urology
topic_unstemmed	misc RC870-923 misc alport syndrome misc novel variants misc digenic alport syndrome misc Diseases of the genitourinary system. Urology
topic_browse	misc RC870-923 misc alport syndrome misc novel variants misc digenic alport syndrome misc Diseases of the genitourinary system. Urology
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title	Novel Digenic Variants in COL4A4 and COL4A5 Causing X-Linked Alport Syndrome: A Case Report
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title_full	Novel Digenic Variants in COL4A4 and COL4A5 Causing X-Linked Alport Syndrome: A Case Report
author_sort	Hideki Uedono
journal	Case Reports in Nephrology and Dialysis
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author_browse	Hideki Uedono Katsuhito Mori Shinya Nakatani Kohei Watanabe Rino Nakaya Fumiyuki Morioka Kazuma Sone Chie Ono Junko Hotta Akihiro Tsuda Naoya Morisada Toshiyuki Seto Kandai Nozu Masanori Emoto
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title_sort	novel digenic variants in col4a4 and col4a5 causing x-linked alport syndrome: a case report
callnumber	RC870-923
title_auth	Novel Digenic Variants in COL4A4 and COL4A5 Causing X-Linked Alport Syndrome: A Case Report
abstract	Introduction: Alport syndrome (AS) is a hereditary, progressive kidney disease characterized by structural abnormalities and dysfunction of the glomerular basement membrane (GBM). AS is classified as X-linked, autosomal, and digenic. The number of cases of digenic AS has increased, but the genotype-phenotype correlation of patient with digenic AS is still unclear. Here, we present a case of digenic AS with novel digenic missense variants in COL4A4 (c.827G>C, p.Gly276Ala) and COL4A5 (c.4369G>C, p.Gly1457Arg). Case Presentation: The patient was a 29-year-old Japanese man suffering from persistent microscopic hematuria and proteinuria without kidney function impairment. Kidney biopsy showed focal interstitial foam cell infiltration, global and segmental glomerulosclerosis. Immunofluorescence staining for collagen IV α5 was almost negative in the GBM and Bowman’s capsule. Electron microscopy revealed irregular thickening with lamellation and segmental thinning of the GBM. Clinical and pathological findings were consistent with AS. Comprehensive next-generation sequencing revealed a heterozygous missense variant in COL4A4 (c.827G>C, p.Gly276Ala) in exon 1 and a hemizygous missense variant in COL4A5 (c.4369G>C, p.Gly1457Arg) in exon 49 on the patient’s paternal and maternal alleles, respectively. The same digenic variants were detected in his sister, and she also showed a similar phenotype. After treatment with angiotensin-converting enzyme inhibitors, proteinuria decreased from 2.3 to 1.1 g/g creatinine, but occult blood persisted. During follow-up, kidney function has been preserved. Conclusion: The novel genotype of our case provides more information on the genotype-phenotype correlation of digenic XLAS, although long-term follow-up is required. The findings in the present case also indicate the importance of genetic tests for family members of a patient diagnosed with digenic AS.
abstractGer	Introduction: Alport syndrome (AS) is a hereditary, progressive kidney disease characterized by structural abnormalities and dysfunction of the glomerular basement membrane (GBM). AS is classified as X-linked, autosomal, and digenic. The number of cases of digenic AS has increased, but the genotype-phenotype correlation of patient with digenic AS is still unclear. Here, we present a case of digenic AS with novel digenic missense variants in COL4A4 (c.827G>C, p.Gly276Ala) and COL4A5 (c.4369G>C, p.Gly1457Arg). Case Presentation: The patient was a 29-year-old Japanese man suffering from persistent microscopic hematuria and proteinuria without kidney function impairment. Kidney biopsy showed focal interstitial foam cell infiltration, global and segmental glomerulosclerosis. Immunofluorescence staining for collagen IV α5 was almost negative in the GBM and Bowman’s capsule. Electron microscopy revealed irregular thickening with lamellation and segmental thinning of the GBM. Clinical and pathological findings were consistent with AS. Comprehensive next-generation sequencing revealed a heterozygous missense variant in COL4A4 (c.827G>C, p.Gly276Ala) in exon 1 and a hemizygous missense variant in COL4A5 (c.4369G>C, p.Gly1457Arg) in exon 49 on the patient’s paternal and maternal alleles, respectively. The same digenic variants were detected in his sister, and she also showed a similar phenotype. After treatment with angiotensin-converting enzyme inhibitors, proteinuria decreased from 2.3 to 1.1 g/g creatinine, but occult blood persisted. During follow-up, kidney function has been preserved. Conclusion: The novel genotype of our case provides more information on the genotype-phenotype correlation of digenic XLAS, although long-term follow-up is required. The findings in the present case also indicate the importance of genetic tests for family members of a patient diagnosed with digenic AS.
abstract_unstemmed	Introduction: Alport syndrome (AS) is a hereditary, progressive kidney disease characterized by structural abnormalities and dysfunction of the glomerular basement membrane (GBM). AS is classified as X-linked, autosomal, and digenic. The number of cases of digenic AS has increased, but the genotype-phenotype correlation of patient with digenic AS is still unclear. Here, we present a case of digenic AS with novel digenic missense variants in COL4A4 (c.827G>C, p.Gly276Ala) and COL4A5 (c.4369G>C, p.Gly1457Arg). Case Presentation: The patient was a 29-year-old Japanese man suffering from persistent microscopic hematuria and proteinuria without kidney function impairment. Kidney biopsy showed focal interstitial foam cell infiltration, global and segmental glomerulosclerosis. Immunofluorescence staining for collagen IV α5 was almost negative in the GBM and Bowman’s capsule. Electron microscopy revealed irregular thickening with lamellation and segmental thinning of the GBM. Clinical and pathological findings were consistent with AS. Comprehensive next-generation sequencing revealed a heterozygous missense variant in COL4A4 (c.827G>C, p.Gly276Ala) in exon 1 and a hemizygous missense variant in COL4A5 (c.4369G>C, p.Gly1457Arg) in exon 49 on the patient’s paternal and maternal alleles, respectively. The same digenic variants were detected in his sister, and she also showed a similar phenotype. After treatment with angiotensin-converting enzyme inhibitors, proteinuria decreased from 2.3 to 1.1 g/g creatinine, but occult blood persisted. During follow-up, kidney function has been preserved. Conclusion: The novel genotype of our case provides more information on the genotype-phenotype correlation of digenic XLAS, although long-term follow-up is required. The findings in the present case also indicate the importance of genetic tests for family members of a patient diagnosed with digenic AS.
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title_short	Novel Digenic Variants in COL4A4 and COL4A5 Causing X-Linked Alport Syndrome: A Case Report
url	https://doi.org/10.1159/000535493 https://doaj.org/article/f5a7078a2df046aa9981ea1649ec053c https://beta.karger.com/Article/FullText/535493 https://doaj.org/toc/2296-9705
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