Intronic variants in inborn errors of metabolism: Beyond the exome
Non-coding regions are areas of the genome that do not directly encode protein and were initially thought to be of little biological relevance. However, subsequent identification of pathogenic variants in these regions indicates there are exceptions to this assertion. With the increasing availabilit...
Ausführliche Beschreibung
Autor*in: |
Ashley Hertzog [verfasserIn] Arthavan Selvanathan [verfasserIn] Elizabeth Farnsworth [verfasserIn] Michel Tchan [verfasserIn] Louisa Adams [verfasserIn] Katherine Lewis [verfasserIn] Adviye Ayper Tolun [verfasserIn] Bruce Bennetts [verfasserIn] Gladys Ho [verfasserIn] Kaustuv Bhattacharya [verfasserIn] |
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Format: |
E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2022 |
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Schlagwörter: |
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Übergeordnetes Werk: |
In: Frontiers in Genetics - Frontiers Media S.A., 2011, 13(2022) |
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Übergeordnetes Werk: |
volume:13 ; year:2022 |
Links: |
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DOI / URN: |
10.3389/fgene.2022.1031495 |
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Katalog-ID: |
DOAJ085474762 |
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10.3389/fgene.2022.1031495 doi (DE-627)DOAJ085474762 (DE-599)DOAJa3aeb52c55d6400097248becbaff14a6 DE-627 ger DE-627 rakwb eng QH426-470 Ashley Hertzog verfasserin aut Intronic variants in inborn errors of metabolism: Beyond the exome 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Non-coding regions are areas of the genome that do not directly encode protein and were initially thought to be of little biological relevance. However, subsequent identification of pathogenic variants in these regions indicates there are exceptions to this assertion. With the increasing availability of next generation sequencing, variants in non-coding regions are often considered when no causative exonic changes have been identified. There is still a lack of understanding of normal human variation in non-coding areas. As a result, potentially pathogenic non-coding variants are initially classified as variants of uncertain significance or are even overlooked during genomic analysis. In most cases where the phenotype is non-specific, clinical suspicion is not sufficient to warrant further exploration of these changes, partly due to the magnitude of non-coding variants identified. In contrast, inborn errors of metabolism (IEMs) are one group of genetic disorders where there is often high phenotypic specificity. The clinical and biochemical features seen often result in a narrow list of diagnostic possibilities. In this context, there have been numerous cases in which suspicion of a particular IEM led to the discovery of a variant in a non-coding region. We present four patients with IEMs where the molecular aetiology was identified within non-coding regions. Confirmation of the molecular diagnosis is often aided by the clinical and biochemical specificity associated with IEMs. Whilst the clinical severity associated with a non-coding variant can be difficult to predict, obtaining a molecular diagnosis is crucial as it ends diagnostic odysseys and assists in management. inborn error of metabolism intronic variant non-coding variant genotype-phenotype correlation promoter variant Genetics Ashley Hertzog verfasserin aut Arthavan Selvanathan verfasserin aut Elizabeth Farnsworth verfasserin aut Michel Tchan verfasserin aut Louisa Adams verfasserin aut Katherine Lewis verfasserin aut Adviye Ayper Tolun verfasserin aut Adviye Ayper Tolun verfasserin aut Bruce Bennetts verfasserin aut Bruce Bennetts verfasserin aut Gladys Ho verfasserin aut Gladys Ho verfasserin aut Kaustuv Bhattacharya verfasserin aut Kaustuv Bhattacharya verfasserin aut In Frontiers in Genetics Frontiers Media S.A., 2011 13(2022) (DE-627)65799829X (DE-600)2606823-0 16648021 nnns volume:13 year:2022 https://doi.org/10.3389/fgene.2022.1031495 kostenfrei https://doaj.org/article/a3aeb52c55d6400097248becbaff14a6 kostenfrei https://www.frontiersin.org/articles/10.3389/fgene.2022.1031495/full kostenfrei https://doaj.org/toc/1664-8021 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_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 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_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 |
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Non-coding regions are areas of the genome that do not directly encode protein and were initially thought to be of little biological relevance. However, subsequent identification of pathogenic variants in these regions indicates there are exceptions to this assertion. With the increasing availability of next generation sequencing, variants in non-coding regions are often considered when no causative exonic changes have been identified. There is still a lack of understanding of normal human variation in non-coding areas. As a result, potentially pathogenic non-coding variants are initially classified as variants of uncertain significance or are even overlooked during genomic analysis. In most cases where the phenotype is non-specific, clinical suspicion is not sufficient to warrant further exploration of these changes, partly due to the magnitude of non-coding variants identified. In contrast, inborn errors of metabolism (IEMs) are one group of genetic disorders where there is often high phenotypic specificity. The clinical and biochemical features seen often result in a narrow list of diagnostic possibilities. In this context, there have been numerous cases in which suspicion of a particular IEM led to the discovery of a variant in a non-coding region. We present four patients with IEMs where the molecular aetiology was identified within non-coding regions. Confirmation of the molecular diagnosis is often aided by the clinical and biochemical specificity associated with IEMs. Whilst the clinical severity associated with a non-coding variant can be difficult to predict, obtaining a molecular diagnosis is crucial as it ends diagnostic odysseys and assists in management. |
abstractGer |
Non-coding regions are areas of the genome that do not directly encode protein and were initially thought to be of little biological relevance. However, subsequent identification of pathogenic variants in these regions indicates there are exceptions to this assertion. With the increasing availability of next generation sequencing, variants in non-coding regions are often considered when no causative exonic changes have been identified. There is still a lack of understanding of normal human variation in non-coding areas. As a result, potentially pathogenic non-coding variants are initially classified as variants of uncertain significance or are even overlooked during genomic analysis. In most cases where the phenotype is non-specific, clinical suspicion is not sufficient to warrant further exploration of these changes, partly due to the magnitude of non-coding variants identified. In contrast, inborn errors of metabolism (IEMs) are one group of genetic disorders where there is often high phenotypic specificity. The clinical and biochemical features seen often result in a narrow list of diagnostic possibilities. In this context, there have been numerous cases in which suspicion of a particular IEM led to the discovery of a variant in a non-coding region. We present four patients with IEMs where the molecular aetiology was identified within non-coding regions. Confirmation of the molecular diagnosis is often aided by the clinical and biochemical specificity associated with IEMs. Whilst the clinical severity associated with a non-coding variant can be difficult to predict, obtaining a molecular diagnosis is crucial as it ends diagnostic odysseys and assists in management. |
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Non-coding regions are areas of the genome that do not directly encode protein and were initially thought to be of little biological relevance. However, subsequent identification of pathogenic variants in these regions indicates there are exceptions to this assertion. With the increasing availability of next generation sequencing, variants in non-coding regions are often considered when no causative exonic changes have been identified. There is still a lack of understanding of normal human variation in non-coding areas. As a result, potentially pathogenic non-coding variants are initially classified as variants of uncertain significance or are even overlooked during genomic analysis. In most cases where the phenotype is non-specific, clinical suspicion is not sufficient to warrant further exploration of these changes, partly due to the magnitude of non-coding variants identified. In contrast, inborn errors of metabolism (IEMs) are one group of genetic disorders where there is often high phenotypic specificity. The clinical and biochemical features seen often result in a narrow list of diagnostic possibilities. In this context, there have been numerous cases in which suspicion of a particular IEM led to the discovery of a variant in a non-coding region. We present four patients with IEMs where the molecular aetiology was identified within non-coding regions. Confirmation of the molecular diagnosis is often aided by the clinical and biochemical specificity associated with IEMs. Whilst the clinical severity associated with a non-coding variant can be difficult to predict, obtaining a molecular diagnosis is crucial as it ends diagnostic odysseys and assists in management. |
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In this context, there have been numerous cases in which suspicion of a particular IEM led to the discovery of a variant in a non-coding region. We present four patients with IEMs where the molecular aetiology was identified within non-coding regions. Confirmation of the molecular diagnosis is often aided by the clinical and biochemical specificity associated with IEMs. Whilst the clinical severity associated with a non-coding variant can be difficult to predict, obtaining a molecular diagnosis is crucial as it ends diagnostic odysseys and assists in management.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">inborn error of metabolism</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">intronic variant</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">non-coding variant</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">genotype-phenotype correlation</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">promoter variant</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Genetics</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield 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