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| Imprinting disorders v0.13 | KCNQ1 |
Anna Le Fevre changed review comment from: Proposed classification: Amber, pending further evidence. The KCNQ1OT1:TSS DMR (imprinting control region 2; IC2) at 11p15.5 is located within KCNQ1 intron 10. IC2 corresponds to the promoter of the long noncoding RNA KCNQ1OT1 and is methylated and inactive on the maternal chromosome. On the paternal chromosome, KCNQ1OT1 is transcribed and represses in cis the flanking imprinted genes, including the growth inhibitor CDKN1C, which is normally transcribed from the maternal allele. In 50% of the Beckwith-Wiedemann Syndrome (BWS) patients, loss of methylation (LOM) of IC2 leads to biallelic expression of KCNQ1OT1 and biallelic silencing of CDKN1C (PMID 30635621). Pathogenic variants in KCNQ1 are associated with long-QT syndrome (LQTS) and can be inherited on the paternal or maternal allele. Loss of methylation (LOM) of IC2 has been reported in a small number of individuals with KCNQ1 germline variants which additionally cause LQTS. Valente et al (PMID 30635621) reported three individuals with LQTS, features of BWS and LOM at IC2 and maternally inherited KCNQ1 variants, two of which were demonstrated to affect KCNQ1 transcription upstream of IC2. Essinger et al (PMID 32393365) analysed KCNQ1 in 52 individuals with LOM at IC2 and identified one individual with a splice site variant causing premature transcription termination. Microdeletions of IC2 variably involving KCNQ1, CDKN1C and KCNQ1OT1 on the maternal allele have been identified in a small number of patients with BWS. LoF in CDKN1C is a known cause of BWS. Beygo et al (PMID 30778172) demonstrated that disruption of KCNQ1 prevents methylation of IC2 supporting the hypothesis that transcription of KCNQ1 is required for establishing the maternal methylation imprint at IC2. Sources: Literature; to: Proposed classification: Amber, pending further evidence. The KCNQ1OT1:TSS DMR (imprinting control region 2; IC2) at 11p15.5 is located within KCNQ1 intron 10. IC2 corresponds to the promoter of the long noncoding RNA KCNQ1OT1 and is methylated and inactive on the maternal chromosome. On the paternal chromosome, KCNQ1OT1 is transcribed and represses in cis the flanking imprinted genes, including the growth inhibitor CDKN1C, which is normally transcribed from the maternal allele. In 50% of the Beckwith-Wiedemann Syndrome (BWS) patients, loss of methylation (LOM) of IC2 leads to biallelic expression of KCNQ1OT1 and biallelic silencing of CDKN1C (PMID 30635621). Pathogenic variants in KCNQ1 are associated with long-QT syndrome (LQTS) and can be inherited on the paternal or maternal allele. Loss of methylation (LOM) of IC2 has been reported in a small number of individuals with KCNQ1 germline variants which additionally cause LQTS. Valente et al (PMID 30635621) reported three individuals with LQTS, features of BWS and LOM at IC2 and maternally inherited KCNQ1 variants, two of which were demonstrated to affect KCNQ1 transcription upstream of IC2. Essinger et al (PMID 32393365) analysed KCNQ1 in 52 individuals with LOM at IC2 and identified one individual with a splice site variant causing premature transcription termination. Microdeletions of IC2 variably involving KCNQ1, CDKN1C and KCNQ1OT1 on the maternal allele have been identified in a small number of patients with BWS. Maternally inherited LoF variants in CDKN1C are a known cause of BWS. Beygo et al (PMID 30778172) demonstrated that disruption of KCNQ1 prevents methylation of IC2 supporting the hypothesis that transcription of KCNQ1 is required for establishing the maternal methylation imprint at IC2. Sources: Literature |
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| Imprinting disorders v0.13 | KCNQ1OT1 |
Anna Le Fevre changed review comment from: Proposed classification: Amber, pending further evidence that isolated intragenic variation in KCNQ1OT1 is definitively associated with a phenotype. KCNQ1OT1 encodes the regulatory antisense non-coding RNA KCNQ1OT1 (KCNQ1 overlapping) and is located within the KCNQ1OT1:TSS DMR (imprinting control region 2; IC2) at 11p15.5. IC2 is located within KCNQ1 intron 10. KCNQ1OT1 is maternally imprinted and paternally expressed. On the paternal chromosome, KCNQ1OT1 is transcribed and represses in cis the flanking imprinted genes, including the growth inhibitor CDKN1C, which is normally transcribed from the maternal allele. In 50% of the BWS patients, loss of methylation (LOM) of IC2 leads to biallelic expression of KCNQ1OT1 and biallelic silencing of CDKN1C (PMID 30635621). Single nucleotide variants within KCNQ1OT1 have not been definitively associated with human disease. A heterozygous maternally inherited non-coding variant was identified in an individual with isolated omphalocele. This variant was shown to alter the methylation pattern of the imprinted allele (PMID 29047350). Eggerman et al (PMID 32447323) described a 132 base pair deletion within KCNQ1OT1 associated with growth retardation in the case of paternal but not maternal transmission. This intragenic deletion did not affect IC2 methylation. Microdeletions of IC2 involving KCNQ1OT1 on the paternal allele have been identified in a small number of patients with Russell-Silver syndrome. Similarly, microdeletions of IC2 involving KCNQ1OT1 on the maternal allele have been identified in a small number of patients with BWS. These deletions also variably involve KCNQ1 or CDKN1C. LoF in CDKN1C is a known cause of BWS. There is some evidence to suggest that disruption of KCNQ1 prevents maternal methylation at IC2 (PMID 30778172). ; to: Proposed classification: Amber, pending further evidence that isolated intragenic variation in KCNQ1OT1 is definitively associated with a phenotype. KCNQ1OT1 encodes the regulatory antisense non-coding RNA KCNQ1OT1 (KCNQ1 overlapping) and is located within the KCNQ1OT1:TSS DMR (imprinting control region 2; IC2) at 11p15.5. IC2 is located within KCNQ1 intron 10. KCNQ1OT1 is maternally imprinted and paternally expressed. On the paternal chromosome, KCNQ1OT1 is transcribed and represses in cis the flanking imprinted genes, including the growth inhibitor CDKN1C, which is normally transcribed from the maternal allele. In 50% of the BWS patients, loss of methylation (LOM) of IC2 leads to biallelic expression of KCNQ1OT1 and biallelic silencing of CDKN1C (PMID 30635621). Expression is increased in BWS due to IC2 epimutations or paternal UPD. Single nucleotide variants within KCNQ1OT1 have not been definitively associated with human disease. A heterozygous maternally inherited non-coding variant was identified in an individual with isolated omphalocele. This variant was shown to alter the methylation pattern of the imprinted allele (PMID 29047350). Eggerman et al (PMID 32447323) described a 132 base pair deletion within KCNQ1OT1 associated with growth retardation in the case of paternal but not maternal transmission. This intragenic deletion did not affect IC2 methylation. Microdeletions of IC2 involving KCNQ1OT1 on the paternal allele have been identified in a small number of patients with Russell-Silver syndrome. Similarly, microdeletions of IC2 involving KCNQ1OT1 on the maternal allele have been identified in a small number of patients with BWS. These deletions also variably involve KCNQ1 or CDKN1C. LoF in CDKN1C is a known cause of BWS. There is some evidence to suggest that disruption of KCNQ1 prevents maternal methylation at IC2 (PMID 30778172). |
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| Imprinting disorders v0.13 | KCNQ1OT1 |
Anna Le Fevre changed review comment from: Proposed classification: Amber, pending further evidence that isolated intragenic variation in KCNQ1OT1 is definitively associated with a phenotype. KCNQ1OT1 encodes the regulatory antisense non-coding RNA KCNQ1OT1 (KCNQ1 overlapping) and is located within the KCNQ1OT1:TSS DMR (imprinting control region 2; IC2) at 11p15.5. IC2 is located within KCNQ1 intron 10. KCNQ1OT1 is maternally imprinted and paternally expressed. On the paternal chromosome, KCNQ1OT1 is transcribed and represses in cis the flanking imprinted genes, including the growth inhibitor CDKN1C, which is normally transcribed from the maternal allele. In 50% of the BWS patients, loss of methylation (LOM) of IC2 leads to biallelic expression of KCNQ1OT1 and biallelic silencing of CDKN1C. Single nucleotide variants within KCNQ1OT1 have not been definitively associated with human disease. A heterozygous maternally inherited non-coding variant was identified in an individual with isolated omphalocele. This variant was shown to alter the methylation pattern of the imprinted allele (PMID 29047350). Eggerman et al (PMID 32447323) described a 132 base pair deletion within KCNQ1OT1 associated with growth retardation in the case of paternal but not maternal transmission. This intragenic deletion did not affect IC2 methylation. Microdeletions of IC2 involving KCNQ1OT1 on the paternal allele have been identified in a small number of patients with Russell-Silver syndrome. Similarly, microdeletions of IC2 involving KCNQ1OT1 on the maternal allele have been identified in a small number of patients with BWS. These deletions also variably involve KCNQ1 or CDKN1C. LoF in CDKN1C is a known cause of BWS. There is some evidence to suggest that disruption of KCNQ1 prevents maternal methylation at IC2 (PMID 30778172). ; to: Proposed classification: Amber, pending further evidence that isolated intragenic variation in KCNQ1OT1 is definitively associated with a phenotype. KCNQ1OT1 encodes the regulatory antisense non-coding RNA KCNQ1OT1 (KCNQ1 overlapping) and is located within the KCNQ1OT1:TSS DMR (imprinting control region 2; IC2) at 11p15.5. IC2 is located within KCNQ1 intron 10. KCNQ1OT1 is maternally imprinted and paternally expressed. On the paternal chromosome, KCNQ1OT1 is transcribed and represses in cis the flanking imprinted genes, including the growth inhibitor CDKN1C, which is normally transcribed from the maternal allele. In 50% of the BWS patients, loss of methylation (LOM) of IC2 leads to biallelic expression of KCNQ1OT1 and biallelic silencing of CDKN1C (PMID 30635621). Single nucleotide variants within KCNQ1OT1 have not been definitively associated with human disease. A heterozygous maternally inherited non-coding variant was identified in an individual with isolated omphalocele. This variant was shown to alter the methylation pattern of the imprinted allele (PMID 29047350). Eggerman et al (PMID 32447323) described a 132 base pair deletion within KCNQ1OT1 associated with growth retardation in the case of paternal but not maternal transmission. This intragenic deletion did not affect IC2 methylation. Microdeletions of IC2 involving KCNQ1OT1 on the paternal allele have been identified in a small number of patients with Russell-Silver syndrome. Similarly, microdeletions of IC2 involving KCNQ1OT1 on the maternal allele have been identified in a small number of patients with BWS. These deletions also variably involve KCNQ1 or CDKN1C. LoF in CDKN1C is a known cause of BWS. There is some evidence to suggest that disruption of KCNQ1 prevents maternal methylation at IC2 (PMID 30778172). |
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| Imprinting disorders v0.13 | KCNQ1OT1 |
Anna Le Fevre changed review comment from: Proposed classification: Amber, pending further evidence that isolated intragenic variation in KCNQ1OT1 is definitively associated with a phenotype. KCNQ1OT1 encodes the regulatory antisense non-coding RNA KCNQ1OT1 (KCNQ1 overlapping) and is located within the KCNQ1OT1:TSS DMR (imprinting control region 2; IC2) at 11p15.5. IC2 is located within KCNQ1 intron 10. KCNQ1OT1 is maternally imprinted and paternally expressed. On the paternal chromosome, KCNQ1OT1 is transcribed and represses in cis the flanking imprinted genes, including the growth inhibitor CDKN1C, which is normally transcribed from the maternal allele. In 50% of the BWS patients, loss of methylation (LOM) of IC2 leads to biallelic expression of KCNQ1OT1 and biallelic silencing of CDKN1C. Single nucleotide variants within KCNQ1OT1 have not been definitively association with human disease. A heterozygous maternally inherited non-coding variant was identified in an individual with isolated omphalocele. This variant was shown to alter the methylation pattern of the imprinted allele (PMID 29047350). Eggerman et al (PMID 32447323) described a 132 base pair deletion within KCNQ1OT1 associated with growth retardation in the case of paternal but not maternal transmission. This intragenic deletion did not affect IC2 methylation. Microdeletions of IC2 involving KCNQ1OT1 on the paternal allele have been identified in a small number of patients with Russell-Silver syndrome. Similarly, microdeletions of IC2 involving KCNQ1OT1 on the maternal allele have been identified in a small number of patients with BWS. These deletions also variably involve KCNQ1 or CDKN1C. LoF in CDKN1C is a known cause of BWS. There is some evidence to suggest that disruption of KCNQ1 prevents maternal methylation at IC2 (PMID 30778172). ; to: Proposed classification: Amber, pending further evidence that isolated intragenic variation in KCNQ1OT1 is definitively associated with a phenotype. KCNQ1OT1 encodes the regulatory antisense non-coding RNA KCNQ1OT1 (KCNQ1 overlapping) and is located within the KCNQ1OT1:TSS DMR (imprinting control region 2; IC2) at 11p15.5. IC2 is located within KCNQ1 intron 10. KCNQ1OT1 is maternally imprinted and paternally expressed. On the paternal chromosome, KCNQ1OT1 is transcribed and represses in cis the flanking imprinted genes, including the growth inhibitor CDKN1C, which is normally transcribed from the maternal allele. In 50% of the BWS patients, loss of methylation (LOM) of IC2 leads to biallelic expression of KCNQ1OT1 and biallelic silencing of CDKN1C. Single nucleotide variants within KCNQ1OT1 have not been definitively associated with human disease. A heterozygous maternally inherited non-coding variant was identified in an individual with isolated omphalocele. This variant was shown to alter the methylation pattern of the imprinted allele (PMID 29047350). Eggerman et al (PMID 32447323) described a 132 base pair deletion within KCNQ1OT1 associated with growth retardation in the case of paternal but not maternal transmission. This intragenic deletion did not affect IC2 methylation. Microdeletions of IC2 involving KCNQ1OT1 on the paternal allele have been identified in a small number of patients with Russell-Silver syndrome. Similarly, microdeletions of IC2 involving KCNQ1OT1 on the maternal allele have been identified in a small number of patients with BWS. These deletions also variably involve KCNQ1 or CDKN1C. LoF in CDKN1C is a known cause of BWS. There is some evidence to suggest that disruption of KCNQ1 prevents maternal methylation at IC2 (PMID 30778172). |
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| Imprinting disorders v0.13 | KCNQ1OT1 |
Anna Le Fevre changed review comment from: Proposed classification: Amber, pending further evidence that isolated intragenic variation in KCNQ1OT1 is definitively associated with a phenotype. KCNQ1OT1 encodes the regulatory antisense non-coding RNA KCNQ1OT1 (KCNQ1 overlapping) and is located within the KCNQ1OT1:TSS DMR (imprinting control region 2; IC2) at 11p15.5. KCNQ1OT1 is maternally imprinted and paternally expressed. Single nucleotide variants within KCNQ1OT1 have not been definitively association with human disease. A heterozygous maternally inherited non-coding variant was identified in an individual with isolated omphalocele. This variant was shown to alter the methylation pattern of the imprinted allele (PMID 29047350). Eggerman et al (PMID 32447323) described a 132 base pair deletion within KCNQ1OT1 associated with growth retardation in the case of paternal but not maternal transmission. This intragenic deletion did not affect IC2 methylation. Microdeletions of IC2 involving KCNQ1OT1 on the paternal allele have been identified in a small number of patients with Russell-Silver syndrome. Similarly, microdeletions of IC2 involving KCNQ1OT1 on the maternal allele have been identified in a small number of patients with BWS. These deletions also variably involve KCNQ1 or CDKN1C. LoF in CDKN1C is a known cause of BWS. There is some evidence to suggest that disruption of KCNQ1 prevents maternal methylation at IC2 (PMID 30778172). Genomic analysis of KCNQ1OT1 was not recommended as part of the diagnostic algorithm for suspected BWS in a 2018 international consensus review (PMID 29377879).; to: Proposed classification: Amber, pending further evidence that isolated intragenic variation in KCNQ1OT1 is definitively associated with a phenotype. KCNQ1OT1 encodes the regulatory antisense non-coding RNA KCNQ1OT1 (KCNQ1 overlapping) and is located within the KCNQ1OT1:TSS DMR (imprinting control region 2; IC2) at 11p15.5. IC2 is located within KCNQ1 intron 10. KCNQ1OT1 is maternally imprinted and paternally expressed. On the paternal chromosome, KCNQ1OT1 is transcribed and represses in cis the flanking imprinted genes, including the growth inhibitor CDKN1C, which is normally transcribed from the maternal allele. In 50% of the BWS patients, loss of methylation (LOM) of IC2 leads to biallelic expression of KCNQ1OT1 and biallelic silencing of CDKN1C. Single nucleotide variants within KCNQ1OT1 have not been definitively association with human disease. A heterozygous maternally inherited non-coding variant was identified in an individual with isolated omphalocele. This variant was shown to alter the methylation pattern of the imprinted allele (PMID 29047350). Eggerman et al (PMID 32447323) described a 132 base pair deletion within KCNQ1OT1 associated with growth retardation in the case of paternal but not maternal transmission. This intragenic deletion did not affect IC2 methylation. Microdeletions of IC2 involving KCNQ1OT1 on the paternal allele have been identified in a small number of patients with Russell-Silver syndrome. Similarly, microdeletions of IC2 involving KCNQ1OT1 on the maternal allele have been identified in a small number of patients with BWS. These deletions also variably involve KCNQ1 or CDKN1C. LoF in CDKN1C is a known cause of BWS. There is some evidence to suggest that disruption of KCNQ1 prevents maternal methylation at IC2 (PMID 30778172). |
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| Imprinting disorders v0.13 | KCNQ1 |
Anna Le Fevre gene: KCNQ1 was added gene: KCNQ1 was added to Imprinting disorders. Sources: Literature Mode of inheritance for gene: KCNQ1 was set to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed) Publications for gene: KCNQ1 were set to PMID 30635621; 32393365; 30778172 Phenotypes for gene: KCNQ1 were set to Beckwith-Wiedemann Syndrome Penetrance for gene: KCNQ1 were set to unknown Review for gene: KCNQ1 was set to AMBER Added comment: Proposed classification: Amber, pending further evidence. The KCNQ1OT1:TSS DMR (imprinting control region 2; IC2) at 11p15.5 is located within KCNQ1 intron 10. IC2 corresponds to the promoter of the long noncoding RNA KCNQ1OT1 and is methylated and inactive on the maternal chromosome. On the paternal chromosome, KCNQ1OT1 is transcribed and represses in cis the flanking imprinted genes, including the growth inhibitor CDKN1C, which is normally transcribed from the maternal allele. In 50% of the Beckwith-Wiedemann Syndrome (BWS) patients, loss of methylation (LOM) of IC2 leads to biallelic expression of KCNQ1OT1 and biallelic silencing of CDKN1C (PMID 30635621). Pathogenic variants in KCNQ1 are associated with long-QT syndrome (LQTS) and can be inherited on the paternal or maternal allele. Loss of methylation (LOM) of IC2 has been reported in a small number of individuals with KCNQ1 germline variants which additionally cause LQTS. Valente et al (PMID 30635621) reported three individuals with LQTS, features of BWS and LOM at IC2 and maternally inherited KCNQ1 variants, two of which were demonstrated to affect KCNQ1 transcription upstream of IC2. Essinger et al (PMID 32393365) analysed KCNQ1 in 52 individuals with LOM at IC2 and identified one individual with a splice site variant causing premature transcription termination. Microdeletions of IC2 variably involving KCNQ1, CDKN1C and KCNQ1OT1 on the maternal allele have been identified in a small number of patients with BWS. LoF in CDKN1C is a known cause of BWS. Beygo et al (PMID 30778172) demonstrated that disruption of KCNQ1 prevents methylation of IC2 supporting the hypothesis that transcription of KCNQ1 is required for establishing the maternal methylation imprint at IC2. Sources: Literature |
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| Imprinting disorders v0.13 | KCNQ1OT1 |
Anna Le Fevre changed review comment from: Proposed classification: Amber, pending further evidence that isolated intragenic variation in KCNQ1OT1 is definitively associated with a phenotype. KCNQ1OT1 encodes the regulatory antisense non-coding RNA KCNQ1OT1 (KCNQ1 overlapping) and is located within the KCNQ1OT1:TSS DMR (imprinting control region 2; IC2) at 11p15.5. KCNQ1OT1 is maternally imprinted and paternally expressed. Single nucleotide variants within KCNQ1OT1 have not been definitively association with human disease. A heterozygous maternally inherited non-coding variant was identified in an individual with isolated omphalocele. This variant was shown to alter the methylation pattern of the imprinted allele (PMID 29047350). Eggerman et al (PMID 32447323) described a 132 base pair deletion within KCNQ1OT1 associated with growth retardation in the case of paternal but not maternal transmission. This intragenic deletion did not affect IC2 methylation. Microdeletions of IC2 involving KCNQ1OT1 on the paternal allele have been identified in a small number of patients with Russell-Silver syndrome. Similarly, microdeletions of IC2 involving KCNQ1OT1 on the maternal allele have been identified in a small number of patients with BWS. These deletions also variably involve KCNQ1 or CDKN1C. LOF in CDKN1C is a known cause of BWS. There is some evidence to suggest that disruption of KCNQ1 prevents maternal methylation at IC2 (PMID 30778172). Genomic analysis of KCNQ1OT1 was not recommended as part of the diagnostic algorithm for suspected BWS in a 2018 international consensus review (PMID 29377879).; to: Proposed classification: Amber, pending further evidence that isolated intragenic variation in KCNQ1OT1 is definitively associated with a phenotype. KCNQ1OT1 encodes the regulatory antisense non-coding RNA KCNQ1OT1 (KCNQ1 overlapping) and is located within the KCNQ1OT1:TSS DMR (imprinting control region 2; IC2) at 11p15.5. KCNQ1OT1 is maternally imprinted and paternally expressed. Single nucleotide variants within KCNQ1OT1 have not been definitively association with human disease. A heterozygous maternally inherited non-coding variant was identified in an individual with isolated omphalocele. This variant was shown to alter the methylation pattern of the imprinted allele (PMID 29047350). Eggerman et al (PMID 32447323) described a 132 base pair deletion within KCNQ1OT1 associated with growth retardation in the case of paternal but not maternal transmission. This intragenic deletion did not affect IC2 methylation. Microdeletions of IC2 involving KCNQ1OT1 on the paternal allele have been identified in a small number of patients with Russell-Silver syndrome. Similarly, microdeletions of IC2 involving KCNQ1OT1 on the maternal allele have been identified in a small number of patients with BWS. These deletions also variably involve KCNQ1 or CDKN1C. LoF in CDKN1C is a known cause of BWS. There is some evidence to suggest that disruption of KCNQ1 prevents maternal methylation at IC2 (PMID 30778172). Genomic analysis of KCNQ1OT1 was not recommended as part of the diagnostic algorithm for suspected BWS in a 2018 international consensus review (PMID 29377879). |
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| Imprinting disorders v0.13 | KCNQ1OT1 |
Anna Le Fevre changed review comment from: Proposed classification: Amber, pending further evidence that isolated intragenic variation in KCNQ1OT1 is definitively associated with a phenotype. KCNQ1OT1 encodes the regulatory non-coding RNA KCNQ1OT1 and is located within the KCNQ1OT1:TSS DMR (imprinting control region 2; IC2) at 11p15.5. KCNQ1OT1 is maternally imprinted and paternally expressed. Single nucleotide variants within KCNQ1OT1 have not been definitively association with human disease. A heterozygous maternally inherited non-coding variant was identified in an individual with isolated omphalocele. This variant was shown to alter the methylation pattern of the imprinted allele (PMID 29047350). Eggerman et al (PMID 32447323) described a 132 base pair deletion within KCNQ1OT1 associated with growth retardation in the case of paternal but not maternal transmission. This intragenic deletion did not affect IC2 methylation. Microdeletions of IC2 involving KCNQ1OT1 on the paternal allele have been identified in a small number of patients with Russell-Silver syndrome. Similarly, microdeletions of IC2 involving KCNQ1OT1 on the maternal allele have been identified in a small number of patients with BWS. These deletions also variably involved neighboring genes KCNQ1 or CDKN1C. LOF in CDKN1C is a known cause of BWS. There is some evidence to suggest that disruption of KCNQ1 prevents maternal methylation at IC2 (PMID 30778172). Genomic analysis of KCNQ1OT1 was not recommended as part of the diagnostic algorithm for suspected BWS in a 2018 international consensus review (PMID 29377879).; to: Proposed classification: Amber, pending further evidence that isolated intragenic variation in KCNQ1OT1 is definitively associated with a phenotype. KCNQ1OT1 encodes the regulatory antisense non-coding RNA KCNQ1OT1 (KCNQ1 overlapping) and is located within the KCNQ1OT1:TSS DMR (imprinting control region 2; IC2) at 11p15.5. KCNQ1OT1 is maternally imprinted and paternally expressed. Single nucleotide variants within KCNQ1OT1 have not been definitively association with human disease. A heterozygous maternally inherited non-coding variant was identified in an individual with isolated omphalocele. This variant was shown to alter the methylation pattern of the imprinted allele (PMID 29047350). Eggerman et al (PMID 32447323) described a 132 base pair deletion within KCNQ1OT1 associated with growth retardation in the case of paternal but not maternal transmission. This intragenic deletion did not affect IC2 methylation. Microdeletions of IC2 involving KCNQ1OT1 on the paternal allele have been identified in a small number of patients with Russell-Silver syndrome. Similarly, microdeletions of IC2 involving KCNQ1OT1 on the maternal allele have been identified in a small number of patients with BWS. These deletions also variably involve KCNQ1 or CDKN1C. LOF in CDKN1C is a known cause of BWS. There is some evidence to suggest that disruption of KCNQ1 prevents maternal methylation at IC2 (PMID 30778172). Genomic analysis of KCNQ1OT1 was not recommended as part of the diagnostic algorithm for suspected BWS in a 2018 international consensus review (PMID 29377879). |
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| Imprinting disorders v0.4 | CDKN1C | Zornitza Stark Marked gene: CDKN1C as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.4 | CDKN1C | Zornitza Stark Gene: cdkn1c has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.4 | CDKN1C | Zornitza Stark Publications for gene: CDKN1C were set to 10424811; PMID: 8841187; 22205991]; 20503313; 19843502; http://igc.otago.ac.nz/home.html; [15372379; 23511928; 30794780 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.3 | CDKN1C | Zornitza Stark reviewed gene: CDKN1C: Rating: GREEN; Mode of pathogenicity: None; Publications: 10424811, 8841187, 22205991, 20503313, 19843502, 15372379, 23511928, 30794780, 33076988, 31976094, 31497289; Phenotypes: Beckwith-Wiedemann syndrome, MIM# 130650, IMAGe syndrome, MIM# 614732, Silver-Russell syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Imprinting disorders v0.0 | CDKN1C |
Zornitza Stark gene: CDKN1C was added gene: CDKN1C was added to Imprinting disorders. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: CDKN1C was set to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed) Publications for gene: CDKN1C were set to 10424811; PMID: 8841187; 22205991]; 20503313; 19843502; http://igc.otago.ac.nz/home.html; [15372379; 23511928; 30794780 Phenotypes for gene: CDKN1C were set to Affected tissue: all; Phenotype resulting from under expression: Beckwith-Wiedemann Syndrome; Phenotypes resulting from gene over expression: IMAGE syndrome; Silver-Russell Syndrome |
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