Common Variable Immunodeficiency and Neurodevelopmental Delay Due to a 13Mb Deletion on Chromosome 4 Including the NFKB1 Gene: A Case Report

Syndromic immunodeficiencies are a heterogeneous group of inborn errors of immunity that can affect the development of non-immune organs and systems. The genetic basis of these immunodeficiencies is highly diverse, ranging from monogenic defects to large chromosomal aberrations. Antibody deficiency...
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Autor*in:	Clara Franco-Jarava [verfasserIn] Irene Valenzuela [verfasserIn] Jacques G. Riviere [verfasserIn] Marina Garcia-Prat [verfasserIn] Mónica Martínez-Gallo [verfasserIn] Romina Dieli-Crimi [verfasserIn] Neus Castells [verfasserIn] Laura Batlle-Masó [verfasserIn] Pere Soler-Palacin [verfasserIn] Roger Colobran [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	primary immunodeficiencies syndromic immunodeficiencies common variable immunodeficiency nfkb1 chromosomal rearrangements

Übergeordnetes Werk:	In: Frontiers in Immunology - Frontiers Media S.A., 2011, 13(2022)
Übergeordnetes Werk:	volume:13 ; year:2022

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fimmu.2022.897975

Katalog-ID:	DOAJ043380077

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520			\|a Syndromic immunodeficiencies are a heterogeneous group of inborn errors of immunity that can affect the development of non-immune organs and systems. The genetic basis of these immunodeficiencies is highly diverse, ranging from monogenic defects to large chromosomal aberrations. Antibody deficiency is the most prevalent immunological abnormality in patients with syndromic immunodeficiencies caused by chromosomal rearrangements, and usually manifests as a common variable immunodeficiency (CVID)-like phenotype. Here we describe a patient with a complex phenotype, including neurodevelopmental delay, dysmorphic features, malformations, and CVID (hypogammaglobulinemia, reduced pre-switch and switch memory B cells, and impaired vaccine response). Microarray-based comparative genomic hybridization (aCGH) revealed a 13-Mb deletion on chromosome 4q22.2-q24 involving 53 genes, some of which were related to the developmental manifestations in our patient. Although initially none of the affected genes could be linked to his CVID phenotype, subsequent reanalysis identified NFKB1 haploinsufficiency as the cause. This study underscores the value of periodic reanalysis of unsolved genetic studies performed with high-throughput technologies (eg, next-generation sequencing and aCGH). This is important because of the ongoing incorporation of new data establishing the relationship between genes and diseases. In the present case, NFKB1 had not been associated with human disease at the time aCGH was performed. Eight years later, reanalysis of the genes included in the chromosome 4 deletion enabled us to identify NFKB1 haploinsufficiency as the genetic cause of our patient’s CVID. In the future, other genes included in the deletion may be linked to human disease, allowing us to better define the molecular basis of our patient’s complex clinical phenotype.
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allfields	10.3389/fimmu.2022.897975 doi (DE-627)DOAJ043380077 (DE-599)DOAJf2279b5b19ad495ba5282ab285a40b9a DE-627 ger DE-627 rakwb eng RC581-607 Clara Franco-Jarava verfasserin aut Common Variable Immunodeficiency and Neurodevelopmental Delay Due to a 13Mb Deletion on Chromosome 4 Including the NFKB1 Gene: A Case Report 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Syndromic immunodeficiencies are a heterogeneous group of inborn errors of immunity that can affect the development of non-immune organs and systems. The genetic basis of these immunodeficiencies is highly diverse, ranging from monogenic defects to large chromosomal aberrations. Antibody deficiency is the most prevalent immunological abnormality in patients with syndromic immunodeficiencies caused by chromosomal rearrangements, and usually manifests as a common variable immunodeficiency (CVID)-like phenotype. Here we describe a patient with a complex phenotype, including neurodevelopmental delay, dysmorphic features, malformations, and CVID (hypogammaglobulinemia, reduced pre-switch and switch memory B cells, and impaired vaccine response). Microarray-based comparative genomic hybridization (aCGH) revealed a 13-Mb deletion on chromosome 4q22.2-q24 involving 53 genes, some of which were related to the developmental manifestations in our patient. Although initially none of the affected genes could be linked to his CVID phenotype, subsequent reanalysis identified NFKB1 haploinsufficiency as the cause. This study underscores the value of periodic reanalysis of unsolved genetic studies performed with high-throughput technologies (eg, next-generation sequencing and aCGH). This is important because of the ongoing incorporation of new data establishing the relationship between genes and diseases. In the present case, NFKB1 had not been associated with human disease at the time aCGH was performed. Eight years later, reanalysis of the genes included in the chromosome 4 deletion enabled us to identify NFKB1 haploinsufficiency as the genetic cause of our patient’s CVID. In the future, other genes included in the deletion may be linked to human disease, allowing us to better define the molecular basis of our patient’s complex clinical phenotype. primary immunodeficiencies syndromic immunodeficiencies common variable immunodeficiency nfkb1 chromosomal rearrangements Immunologic diseases. Allergy Clara Franco-Jarava verfasserin aut Clara Franco-Jarava verfasserin aut Irene Valenzuela verfasserin aut Irene Valenzuela verfasserin aut Jacques G. Riviere verfasserin aut Jacques G. Riviere verfasserin aut Jacques G. Riviere verfasserin aut Marina Garcia-Prat verfasserin aut Marina Garcia-Prat verfasserin aut Marina Garcia-Prat verfasserin aut Mónica Martínez-Gallo verfasserin aut Mónica Martínez-Gallo verfasserin aut Mónica Martínez-Gallo verfasserin aut Romina Dieli-Crimi verfasserin aut Romina Dieli-Crimi verfasserin aut Romina Dieli-Crimi verfasserin aut Neus Castells verfasserin aut Neus Castells verfasserin aut Laura Batlle-Masó verfasserin aut Laura Batlle-Masó verfasserin aut Pere Soler-Palacin verfasserin aut Pere Soler-Palacin verfasserin aut Pere Soler-Palacin verfasserin aut Roger Colobran verfasserin aut Roger Colobran verfasserin aut Roger Colobran verfasserin aut Roger Colobran verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 13(2022) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:13 year:2022 https://doi.org/10.3389/fimmu.2022.897975 kostenfrei https://doaj.org/article/f2279b5b19ad495ba5282ab285a40b9a kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2022.897975/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 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 13 2022
spelling	10.3389/fimmu.2022.897975 doi (DE-627)DOAJ043380077 (DE-599)DOAJf2279b5b19ad495ba5282ab285a40b9a DE-627 ger DE-627 rakwb eng RC581-607 Clara Franco-Jarava verfasserin aut Common Variable Immunodeficiency and Neurodevelopmental Delay Due to a 13Mb Deletion on Chromosome 4 Including the NFKB1 Gene: A Case Report 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Syndromic immunodeficiencies are a heterogeneous group of inborn errors of immunity that can affect the development of non-immune organs and systems. The genetic basis of these immunodeficiencies is highly diverse, ranging from monogenic defects to large chromosomal aberrations. Antibody deficiency is the most prevalent immunological abnormality in patients with syndromic immunodeficiencies caused by chromosomal rearrangements, and usually manifests as a common variable immunodeficiency (CVID)-like phenotype. Here we describe a patient with a complex phenotype, including neurodevelopmental delay, dysmorphic features, malformations, and CVID (hypogammaglobulinemia, reduced pre-switch and switch memory B cells, and impaired vaccine response). Microarray-based comparative genomic hybridization (aCGH) revealed a 13-Mb deletion on chromosome 4q22.2-q24 involving 53 genes, some of which were related to the developmental manifestations in our patient. Although initially none of the affected genes could be linked to his CVID phenotype, subsequent reanalysis identified NFKB1 haploinsufficiency as the cause. This study underscores the value of periodic reanalysis of unsolved genetic studies performed with high-throughput technologies (eg, next-generation sequencing and aCGH). This is important because of the ongoing incorporation of new data establishing the relationship between genes and diseases. In the present case, NFKB1 had not been associated with human disease at the time aCGH was performed. Eight years later, reanalysis of the genes included in the chromosome 4 deletion enabled us to identify NFKB1 haploinsufficiency as the genetic cause of our patient’s CVID. In the future, other genes included in the deletion may be linked to human disease, allowing us to better define the molecular basis of our patient’s complex clinical phenotype. primary immunodeficiencies syndromic immunodeficiencies common variable immunodeficiency nfkb1 chromosomal rearrangements Immunologic diseases. Allergy Clara Franco-Jarava verfasserin aut Clara Franco-Jarava verfasserin aut Irene Valenzuela verfasserin aut Irene Valenzuela verfasserin aut Jacques G. Riviere verfasserin aut Jacques G. Riviere verfasserin aut Jacques G. Riviere verfasserin aut Marina Garcia-Prat verfasserin aut Marina Garcia-Prat verfasserin aut Marina Garcia-Prat verfasserin aut Mónica Martínez-Gallo verfasserin aut Mónica Martínez-Gallo verfasserin aut Mónica Martínez-Gallo verfasserin aut Romina Dieli-Crimi verfasserin aut Romina Dieli-Crimi verfasserin aut Romina Dieli-Crimi verfasserin aut Neus Castells verfasserin aut Neus Castells verfasserin aut Laura Batlle-Masó verfasserin aut Laura Batlle-Masó verfasserin aut Pere Soler-Palacin verfasserin aut Pere Soler-Palacin verfasserin aut Pere Soler-Palacin verfasserin aut Roger Colobran verfasserin aut Roger Colobran verfasserin aut Roger Colobran verfasserin aut Roger Colobran verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 13(2022) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:13 year:2022 https://doi.org/10.3389/fimmu.2022.897975 kostenfrei https://doaj.org/article/f2279b5b19ad495ba5282ab285a40b9a kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2022.897975/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 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 13 2022
allfields_unstemmed	10.3389/fimmu.2022.897975 doi (DE-627)DOAJ043380077 (DE-599)DOAJf2279b5b19ad495ba5282ab285a40b9a DE-627 ger DE-627 rakwb eng RC581-607 Clara Franco-Jarava verfasserin aut Common Variable Immunodeficiency and Neurodevelopmental Delay Due to a 13Mb Deletion on Chromosome 4 Including the NFKB1 Gene: A Case Report 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Syndromic immunodeficiencies are a heterogeneous group of inborn errors of immunity that can affect the development of non-immune organs and systems. The genetic basis of these immunodeficiencies is highly diverse, ranging from monogenic defects to large chromosomal aberrations. Antibody deficiency is the most prevalent immunological abnormality in patients with syndromic immunodeficiencies caused by chromosomal rearrangements, and usually manifests as a common variable immunodeficiency (CVID)-like phenotype. Here we describe a patient with a complex phenotype, including neurodevelopmental delay, dysmorphic features, malformations, and CVID (hypogammaglobulinemia, reduced pre-switch and switch memory B cells, and impaired vaccine response). Microarray-based comparative genomic hybridization (aCGH) revealed a 13-Mb deletion on chromosome 4q22.2-q24 involving 53 genes, some of which were related to the developmental manifestations in our patient. Although initially none of the affected genes could be linked to his CVID phenotype, subsequent reanalysis identified NFKB1 haploinsufficiency as the cause. This study underscores the value of periodic reanalysis of unsolved genetic studies performed with high-throughput technologies (eg, next-generation sequencing and aCGH). This is important because of the ongoing incorporation of new data establishing the relationship between genes and diseases. In the present case, NFKB1 had not been associated with human disease at the time aCGH was performed. Eight years later, reanalysis of the genes included in the chromosome 4 deletion enabled us to identify NFKB1 haploinsufficiency as the genetic cause of our patient’s CVID. In the future, other genes included in the deletion may be linked to human disease, allowing us to better define the molecular basis of our patient’s complex clinical phenotype. primary immunodeficiencies syndromic immunodeficiencies common variable immunodeficiency nfkb1 chromosomal rearrangements Immunologic diseases. Allergy Clara Franco-Jarava verfasserin aut Clara Franco-Jarava verfasserin aut Irene Valenzuela verfasserin aut Irene Valenzuela verfasserin aut Jacques G. Riviere verfasserin aut Jacques G. Riviere verfasserin aut Jacques G. Riviere verfasserin aut Marina Garcia-Prat verfasserin aut Marina Garcia-Prat verfasserin aut Marina Garcia-Prat verfasserin aut Mónica Martínez-Gallo verfasserin aut Mónica Martínez-Gallo verfasserin aut Mónica Martínez-Gallo verfasserin aut Romina Dieli-Crimi verfasserin aut Romina Dieli-Crimi verfasserin aut Romina Dieli-Crimi verfasserin aut Neus Castells verfasserin aut Neus Castells verfasserin aut Laura Batlle-Masó verfasserin aut Laura Batlle-Masó verfasserin aut Pere Soler-Palacin verfasserin aut Pere Soler-Palacin verfasserin aut Pere Soler-Palacin verfasserin aut Roger Colobran verfasserin aut Roger Colobran verfasserin aut Roger Colobran verfasserin aut Roger Colobran verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 13(2022) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:13 year:2022 https://doi.org/10.3389/fimmu.2022.897975 kostenfrei https://doaj.org/article/f2279b5b19ad495ba5282ab285a40b9a kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2022.897975/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 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 13 2022
allfieldsGer	10.3389/fimmu.2022.897975 doi (DE-627)DOAJ043380077 (DE-599)DOAJf2279b5b19ad495ba5282ab285a40b9a DE-627 ger DE-627 rakwb eng RC581-607 Clara Franco-Jarava verfasserin aut Common Variable Immunodeficiency and Neurodevelopmental Delay Due to a 13Mb Deletion on Chromosome 4 Including the NFKB1 Gene: A Case Report 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Syndromic immunodeficiencies are a heterogeneous group of inborn errors of immunity that can affect the development of non-immune organs and systems. The genetic basis of these immunodeficiencies is highly diverse, ranging from monogenic defects to large chromosomal aberrations. Antibody deficiency is the most prevalent immunological abnormality in patients with syndromic immunodeficiencies caused by chromosomal rearrangements, and usually manifests as a common variable immunodeficiency (CVID)-like phenotype. Here we describe a patient with a complex phenotype, including neurodevelopmental delay, dysmorphic features, malformations, and CVID (hypogammaglobulinemia, reduced pre-switch and switch memory B cells, and impaired vaccine response). Microarray-based comparative genomic hybridization (aCGH) revealed a 13-Mb deletion on chromosome 4q22.2-q24 involving 53 genes, some of which were related to the developmental manifestations in our patient. Although initially none of the affected genes could be linked to his CVID phenotype, subsequent reanalysis identified NFKB1 haploinsufficiency as the cause. This study underscores the value of periodic reanalysis of unsolved genetic studies performed with high-throughput technologies (eg, next-generation sequencing and aCGH). This is important because of the ongoing incorporation of new data establishing the relationship between genes and diseases. In the present case, NFKB1 had not been associated with human disease at the time aCGH was performed. Eight years later, reanalysis of the genes included in the chromosome 4 deletion enabled us to identify NFKB1 haploinsufficiency as the genetic cause of our patient’s CVID. In the future, other genes included in the deletion may be linked to human disease, allowing us to better define the molecular basis of our patient’s complex clinical phenotype. primary immunodeficiencies syndromic immunodeficiencies common variable immunodeficiency nfkb1 chromosomal rearrangements Immunologic diseases. Allergy Clara Franco-Jarava verfasserin aut Clara Franco-Jarava verfasserin aut Irene Valenzuela verfasserin aut Irene Valenzuela verfasserin aut Jacques G. Riviere verfasserin aut Jacques G. Riviere verfasserin aut Jacques G. Riviere verfasserin aut Marina Garcia-Prat verfasserin aut Marina Garcia-Prat verfasserin aut Marina Garcia-Prat verfasserin aut Mónica Martínez-Gallo verfasserin aut Mónica Martínez-Gallo verfasserin aut Mónica Martínez-Gallo verfasserin aut Romina Dieli-Crimi verfasserin aut Romina Dieli-Crimi verfasserin aut Romina Dieli-Crimi verfasserin aut Neus Castells verfasserin aut Neus Castells verfasserin aut Laura Batlle-Masó verfasserin aut Laura Batlle-Masó verfasserin aut Pere Soler-Palacin verfasserin aut Pere Soler-Palacin verfasserin aut Pere Soler-Palacin verfasserin aut Roger Colobran verfasserin aut Roger Colobran verfasserin aut Roger Colobran verfasserin aut Roger Colobran verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 13(2022) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:13 year:2022 https://doi.org/10.3389/fimmu.2022.897975 kostenfrei https://doaj.org/article/f2279b5b19ad495ba5282ab285a40b9a kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2022.897975/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 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 13 2022
allfieldsSound	10.3389/fimmu.2022.897975 doi (DE-627)DOAJ043380077 (DE-599)DOAJf2279b5b19ad495ba5282ab285a40b9a DE-627 ger DE-627 rakwb eng RC581-607 Clara Franco-Jarava verfasserin aut Common Variable Immunodeficiency and Neurodevelopmental Delay Due to a 13Mb Deletion on Chromosome 4 Including the NFKB1 Gene: A Case Report 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Syndromic immunodeficiencies are a heterogeneous group of inborn errors of immunity that can affect the development of non-immune organs and systems. The genetic basis of these immunodeficiencies is highly diverse, ranging from monogenic defects to large chromosomal aberrations. Antibody deficiency is the most prevalent immunological abnormality in patients with syndromic immunodeficiencies caused by chromosomal rearrangements, and usually manifests as a common variable immunodeficiency (CVID)-like phenotype. Here we describe a patient with a complex phenotype, including neurodevelopmental delay, dysmorphic features, malformations, and CVID (hypogammaglobulinemia, reduced pre-switch and switch memory B cells, and impaired vaccine response). Microarray-based comparative genomic hybridization (aCGH) revealed a 13-Mb deletion on chromosome 4q22.2-q24 involving 53 genes, some of which were related to the developmental manifestations in our patient. Although initially none of the affected genes could be linked to his CVID phenotype, subsequent reanalysis identified NFKB1 haploinsufficiency as the cause. This study underscores the value of periodic reanalysis of unsolved genetic studies performed with high-throughput technologies (eg, next-generation sequencing and aCGH). This is important because of the ongoing incorporation of new data establishing the relationship between genes and diseases. In the present case, NFKB1 had not been associated with human disease at the time aCGH was performed. Eight years later, reanalysis of the genes included in the chromosome 4 deletion enabled us to identify NFKB1 haploinsufficiency as the genetic cause of our patient’s CVID. In the future, other genes included in the deletion may be linked to human disease, allowing us to better define the molecular basis of our patient’s complex clinical phenotype. primary immunodeficiencies syndromic immunodeficiencies common variable immunodeficiency nfkb1 chromosomal rearrangements Immunologic diseases. Allergy Clara Franco-Jarava verfasserin aut Clara Franco-Jarava verfasserin aut Irene Valenzuela verfasserin aut Irene Valenzuela verfasserin aut Jacques G. Riviere verfasserin aut Jacques G. Riviere verfasserin aut Jacques G. Riviere verfasserin aut Marina Garcia-Prat verfasserin aut Marina Garcia-Prat verfasserin aut Marina Garcia-Prat verfasserin aut Mónica Martínez-Gallo verfasserin aut Mónica Martínez-Gallo verfasserin aut Mónica Martínez-Gallo verfasserin aut Romina Dieli-Crimi verfasserin aut Romina Dieli-Crimi verfasserin aut Romina Dieli-Crimi verfasserin aut Neus Castells verfasserin aut Neus Castells verfasserin aut Laura Batlle-Masó verfasserin aut Laura Batlle-Masó verfasserin aut Pere Soler-Palacin verfasserin aut Pere Soler-Palacin verfasserin aut Pere Soler-Palacin verfasserin aut Roger Colobran verfasserin aut Roger Colobran verfasserin aut Roger Colobran verfasserin aut Roger Colobran verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 13(2022) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:13 year:2022 https://doi.org/10.3389/fimmu.2022.897975 kostenfrei https://doaj.org/article/f2279b5b19ad495ba5282ab285a40b9a kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2022.897975/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 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 13 2022
language	English
source	In Frontiers in Immunology 13(2022) volume:13 year:2022
sourceStr	In Frontiers in Immunology 13(2022) volume:13 year:2022
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	primary immunodeficiencies syndromic immunodeficiencies common variable immunodeficiency nfkb1 chromosomal rearrangements Immunologic diseases. Allergy
isfreeaccess_bool	true
container_title	Frontiers in Immunology
authorswithroles_txt_mv	Clara Franco-Jarava @@aut@@ Irene Valenzuela @@aut@@ Jacques G. Riviere @@aut@@ Marina Garcia-Prat @@aut@@ Mónica Martínez-Gallo @@aut@@ Romina Dieli-Crimi @@aut@@ Neus Castells @@aut@@ Laura Batlle-Masó @@aut@@ Pere Soler-Palacin @@aut@@ Roger Colobran @@aut@@
publishDateDaySort_date	2022-01-01T00:00:00Z
hierarchy_top_id	657998354
id	DOAJ043380077
language_de	englisch
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callnumber-first	R - Medicine
author	Clara Franco-Jarava
spellingShingle	Clara Franco-Jarava misc RC581-607 misc primary immunodeficiencies misc syndromic immunodeficiencies misc common variable immunodeficiency misc nfkb1 misc chromosomal rearrangements misc Immunologic diseases. Allergy Common Variable Immunodeficiency and Neurodevelopmental Delay Due to a 13Mb Deletion on Chromosome 4 Including the NFKB1 Gene: A Case Report
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topic_title	RC581-607 Common Variable Immunodeficiency and Neurodevelopmental Delay Due to a 13Mb Deletion on Chromosome 4 Including the NFKB1 Gene: A Case Report primary immunodeficiencies syndromic immunodeficiencies common variable immunodeficiency nfkb1 chromosomal rearrangements
topic	misc RC581-607 misc primary immunodeficiencies misc syndromic immunodeficiencies misc common variable immunodeficiency misc nfkb1 misc chromosomal rearrangements misc Immunologic diseases. Allergy
topic_unstemmed	misc RC581-607 misc primary immunodeficiencies misc syndromic immunodeficiencies misc common variable immunodeficiency misc nfkb1 misc chromosomal rearrangements misc Immunologic diseases. Allergy
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title	Common Variable Immunodeficiency and Neurodevelopmental Delay Due to a 13Mb Deletion on Chromosome 4 Including the NFKB1 Gene: A Case Report
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title_full	Common Variable Immunodeficiency and Neurodevelopmental Delay Due to a 13Mb Deletion on Chromosome 4 Including the NFKB1 Gene: A Case Report
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author_browse	Clara Franco-Jarava Irene Valenzuela Jacques G. Riviere Marina Garcia-Prat Mónica Martínez-Gallo Romina Dieli-Crimi Neus Castells Laura Batlle-Masó Pere Soler-Palacin Roger Colobran
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title_sort	common variable immunodeficiency and neurodevelopmental delay due to a 13mb deletion on chromosome 4 including the nfkb1 gene: a case report
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title_auth	Common Variable Immunodeficiency and Neurodevelopmental Delay Due to a 13Mb Deletion on Chromosome 4 Including the NFKB1 Gene: A Case Report
abstract	Syndromic immunodeficiencies are a heterogeneous group of inborn errors of immunity that can affect the development of non-immune organs and systems. The genetic basis of these immunodeficiencies is highly diverse, ranging from monogenic defects to large chromosomal aberrations. Antibody deficiency is the most prevalent immunological abnormality in patients with syndromic immunodeficiencies caused by chromosomal rearrangements, and usually manifests as a common variable immunodeficiency (CVID)-like phenotype. Here we describe a patient with a complex phenotype, including neurodevelopmental delay, dysmorphic features, malformations, and CVID (hypogammaglobulinemia, reduced pre-switch and switch memory B cells, and impaired vaccine response). Microarray-based comparative genomic hybridization (aCGH) revealed a 13-Mb deletion on chromosome 4q22.2-q24 involving 53 genes, some of which were related to the developmental manifestations in our patient. Although initially none of the affected genes could be linked to his CVID phenotype, subsequent reanalysis identified NFKB1 haploinsufficiency as the cause. This study underscores the value of periodic reanalysis of unsolved genetic studies performed with high-throughput technologies (eg, next-generation sequencing and aCGH). This is important because of the ongoing incorporation of new data establishing the relationship between genes and diseases. In the present case, NFKB1 had not been associated with human disease at the time aCGH was performed. Eight years later, reanalysis of the genes included in the chromosome 4 deletion enabled us to identify NFKB1 haploinsufficiency as the genetic cause of our patient’s CVID. In the future, other genes included in the deletion may be linked to human disease, allowing us to better define the molecular basis of our patient’s complex clinical phenotype.
abstractGer	Syndromic immunodeficiencies are a heterogeneous group of inborn errors of immunity that can affect the development of non-immune organs and systems. The genetic basis of these immunodeficiencies is highly diverse, ranging from monogenic defects to large chromosomal aberrations. Antibody deficiency is the most prevalent immunological abnormality in patients with syndromic immunodeficiencies caused by chromosomal rearrangements, and usually manifests as a common variable immunodeficiency (CVID)-like phenotype. Here we describe a patient with a complex phenotype, including neurodevelopmental delay, dysmorphic features, malformations, and CVID (hypogammaglobulinemia, reduced pre-switch and switch memory B cells, and impaired vaccine response). Microarray-based comparative genomic hybridization (aCGH) revealed a 13-Mb deletion on chromosome 4q22.2-q24 involving 53 genes, some of which were related to the developmental manifestations in our patient. Although initially none of the affected genes could be linked to his CVID phenotype, subsequent reanalysis identified NFKB1 haploinsufficiency as the cause. This study underscores the value of periodic reanalysis of unsolved genetic studies performed with high-throughput technologies (eg, next-generation sequencing and aCGH). This is important because of the ongoing incorporation of new data establishing the relationship between genes and diseases. In the present case, NFKB1 had not been associated with human disease at the time aCGH was performed. Eight years later, reanalysis of the genes included in the chromosome 4 deletion enabled us to identify NFKB1 haploinsufficiency as the genetic cause of our patient’s CVID. In the future, other genes included in the deletion may be linked to human disease, allowing us to better define the molecular basis of our patient’s complex clinical phenotype.
abstract_unstemmed	Syndromic immunodeficiencies are a heterogeneous group of inborn errors of immunity that can affect the development of non-immune organs and systems. The genetic basis of these immunodeficiencies is highly diverse, ranging from monogenic defects to large chromosomal aberrations. Antibody deficiency is the most prevalent immunological abnormality in patients with syndromic immunodeficiencies caused by chromosomal rearrangements, and usually manifests as a common variable immunodeficiency (CVID)-like phenotype. Here we describe a patient with a complex phenotype, including neurodevelopmental delay, dysmorphic features, malformations, and CVID (hypogammaglobulinemia, reduced pre-switch and switch memory B cells, and impaired vaccine response). Microarray-based comparative genomic hybridization (aCGH) revealed a 13-Mb deletion on chromosome 4q22.2-q24 involving 53 genes, some of which were related to the developmental manifestations in our patient. Although initially none of the affected genes could be linked to his CVID phenotype, subsequent reanalysis identified NFKB1 haploinsufficiency as the cause. This study underscores the value of periodic reanalysis of unsolved genetic studies performed with high-throughput technologies (eg, next-generation sequencing and aCGH). This is important because of the ongoing incorporation of new data establishing the relationship between genes and diseases. In the present case, NFKB1 had not been associated with human disease at the time aCGH was performed. Eight years later, reanalysis of the genes included in the chromosome 4 deletion enabled us to identify NFKB1 haploinsufficiency as the genetic cause of our patient’s CVID. In the future, other genes included in the deletion may be linked to human disease, allowing us to better define the molecular basis of our patient’s complex clinical phenotype.
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title_short	Common Variable Immunodeficiency and Neurodevelopmental Delay Due to a 13Mb Deletion on Chromosome 4 Including the NFKB1 Gene: A Case Report
url	https://doi.org/10.3389/fimmu.2022.897975 https://doaj.org/article/f2279b5b19ad495ba5282ab285a40b9a https://www.frontiersin.org/articles/10.3389/fimmu.2022.897975/full https://doaj.org/toc/1664-3224
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Common Variable Immunodeficiency and Neurodevelopmental Delay Due to a 13Mb Deletion on Chromosome 4 Including the NFKB1 Gene: A Case Report

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