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| Early onset or syndromic epilepsy v5.6 | CRELD1 | Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to'BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v5.6 | CRELD1 | Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: CRELD1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v5.6 | CRELD1 | Eleanor Williams reviewed gene: CRELD1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v5.5 | CRELD1 |
Achchuthan Shanmugasundram Source NHS GMS was added to CRELD1. Source Expert Review Green was added to CRELD1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
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| Early onset or syndromic epilepsy v4.102 | CRELD1 | Sarah Leigh Tag Q3_23_promote_green tag was added to gene: CRELD1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v4.102 | CRELD1 | Sarah Leigh edited their review of gene: CRELD1: Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v4.102 | CRELD1 | Sarah Leigh Classified gene: CRELD1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v4.102 | CRELD1 | Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v4.102 | CRELD1 | Sarah Leigh Gene: creld1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v4.101 | CRELD1 |
Sarah Leigh changed review comment from: Personal communication from Natalie Trump There are now a total of 18 affected probands (14 families) with recessive variants in CRELD1 : 16 with a frameshift in trans with a missense variant 1 homozygous for a commonly recurrent missense variant (C192Y) 1 compound heterozygous for two missense variants (C192Y & A391P) 0 homozygous or compound het for putative null alleles This data has been submitted for publication All 18 probands has epilepsy, hypotonia, speech delay and motor delay.; to: Personal communication from Natalie Trump There are now a total of 18 affected probands (14 families) with recessive variants in CRELD1 : 16 with a frameshift in trans with a missense variant 1 homozygous for a commonly recurrent missense variant (C192Y) 1 compound heterozygous for two missense variants (C192Y & A391P) 0 homozygous or compound het for putative null alleles This data has been accepted for publication. All 18 probands has epilepsy, hypotonia, speech delay and motor delay. |
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| Early onset or syndromic epilepsy v4.94 | CRELD1 |
Sarah Leigh changed review comment from: Personal communication from Natalie Trump There are now a total of 18 affected probands (14 families) with recessive variants in CRELD1 : 16 with a frameshift in trans with a missense variant 1 homozygous for a commonly recurrent missense variant (C192Y) 1 compound heterozygous for two missense variants (C192Y & A391P) 0 homozygous or compound het for putative null alleles All 18 probands has epilepsy, hypotonia, speech delay and motor delay.; to: Personal communication from Natalie Trump There are now a total of 18 affected probands (14 families) with recessive variants in CRELD1 : 16 with a frameshift in trans with a missense variant 1 homozygous for a commonly recurrent missense variant (C192Y) 1 compound heterozygous for two missense variants (C192Y & A391P) 0 homozygous or compound het for putative null alleles This data has been submitted for publication All 18 probands has epilepsy, hypotonia, speech delay and motor delay. |
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| Early onset or syndromic epilepsy v4.94 | CRELD1 |
Sarah Leigh changed review comment from: Personal communication from Natalie Trump There are now a total of 18 affected probands (14 families) with recessive variants in CRELD1 : 16 with a frameshift in trans with a missense variant 1 homozygous for a commonly recurrent missense variant (C192Y) 1 compound heterozygous for two missense variants (C192Y & A391P) 0 homozygous or compound het for putative null alleles All 18 probands has epilepsy, hypotonia, speech delay and motor delay.; to: Personal communication from Natalie Trump There are now a total of 18 affected probands (14 families) with recessive variants in CRELD1 : 16 with a frameshift in trans with a missense variant 1 homozygous for a commonly recurrent missense variant (C192Y) 1 compound heterozygous for two missense variants (C192Y & A391P) 0 homozygous or compound het for putative null alleles All 18 probands has epilepsy, hypotonia, speech delay and motor delay. |
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| Early onset or syndromic epilepsy v4.94 | CRELD1 |
Sarah Leigh commented on gene: CRELD1: Personal communication from Natalie Trump There are now a total of 18 affected probands (14 families) with recessive variants in CRELD1 : 16 with a frameshift in trans with a missense variant 1 homozygous for a commonly recurrent missense variant (C192Y) 1 compound heterozygous for two missense variants (C192Y & A391P) 0 homozygous or compound het for putative null alleles All 18 probands has epilepsy, hypotonia, speech delay and motor delay. |
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| Early onset or syndromic epilepsy v4.94 | CRELD1 | Sarah Leigh reviewed gene: CRELD1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v4.94 | CRELD1 | Sarah Leigh Classified gene: CRELD1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v4.94 | CRELD1 | Sarah Leigh Gene: creld1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v4.93 | CRELD1 | Sarah Leigh Publications for gene: CRELD1 were set to PMID 32437232 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v4.87 | CRELD1 | Sarah Leigh Phenotypes for gene: CRELD1 were changed from Developmental epileptic encephalopathy; intractable seizures; global developmental delay and cognitive delay; treatment resistant epileptic seizures; adrenal insufficiency; severe bilateral neural hearing loss; immature eye development; acute respiratory distress; submucosal cleft palate to Atrioventricular septal defect, partial, with heterotaxy syndrome, OMIM:606217; {Atrioventricular septal defect, susceptibility to, 2}, OMIM:606217; atrioventricular septal defect, susceptibility to, 2, MONDO:0011650 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v2.558 | CRELD1 | Ivone Leong Added comment: Comment on phenotypes: Changed from "neurodevelopmental disorder;treatment resistant epileptic seizures;mild to severe developmental and cognitive delays;adrenal insufficiency;severe bilateral neural hearing loss;immature eye development;accuse respiratory distress and submucosal cleft palate" to "Developmental epileptic encephalopathy; intractable seizures; global developmental delay and cognitive delay; treatment resistant epileptic seizures; adrenal insufficiency; severe bilateral neural hearing loss; immature eye development; acute respiratory distress; submucosal cleft palate" for Natalie Trump (Congenica) as the first option was entered by mistake. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v2.558 | CRELD1 | Ivone Leong Phenotypes for gene: CRELD1 were changed from neurodevelopmental disorder; treatment resistant epileptic seizures; mild to severe developmental and cognitive delays; adrenal insufficiency; severe bilateral neural hearing loss; immature eye development; accuse respiratory distress and submucosal cleft palate to Developmental epileptic encephalopathy; intractable seizures; global developmental delay and cognitive delay; treatment resistant epileptic seizures; adrenal insufficiency; severe bilateral neural hearing loss; immature eye development; acute respiratory distress; submucosal cleft palate | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v2.557 | CRELD1 | Ivone Leong Added comment: Comment on mode of inheritance: Changed from "BOTH monoallelic and biallelic, autosomal or pseudoautosomal" to "BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal" for Natalie Trump (Congenica) as the first option was entered by mistake. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v2.557 | CRELD1 | Ivone Leong Mode of inheritance for gene: CRELD1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v2.554 | CRELD1 | Natalie Trump reviewed gene: CRELD1: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 32437232; Phenotypes: Developmental epileptic encephalopathy, intractable seizures, global developmental delay and cognitive delay, treatment resistant epileptic seizures, adrenal insufficiency, severe bilateral neural hearing loss, immature eye development, acute respiratory distress, submucosal cleft palate; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v2.554 | CRELD1 | Natalie Trump Deleted their review | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Early onset or syndromic epilepsy v2.554 | CRELD1 |
Natalie Trump gene: CRELD1 was added gene: CRELD1 was added to Genetic epilepsy syndromes. Sources: Expert Review Mode of inheritance for gene: CRELD1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: CRELD1 were set to PMID 32437232 Phenotypes for gene: CRELD1 were set to neurodevelopmental disorder; treatment resistant epileptic seizures; mild to severe developmental and cognitive delays; adrenal insufficiency; severe bilateral neural hearing loss; immature eye development; accuse respiratory distress and submucosal cleft palate Penetrance for gene: CRELD1 were set to Incomplete Mode of pathogenicity for gene: CRELD1 was set to Other Review for gene: CRELD1 was set to GREEN gene: CRELD1 was marked as current diagnostic Added comment: Heterozygous variants in CRELD1 are known to be associated with susceptibility to atrioventricular septal defect (AVSD), AVSD2 and AVSD associated with heterotaxy syndrome. Unaffected carriers have been reported suggesting reduced penetrance for this phenotype (OMIM 606217) . Unpublished data has recently identified 9 unrelated families (including 3 families with 2 affected siblings each) with biallelic CRELD1 variants. The most common features in these children with biallelic CRELD1 variants is intractable seizures. Other features include global developmental delay and cognitive delay, treatment resistant epileptic seizures, adrenal insufficiency, severe bilateral neural hearing loss, immature eye development, accute respiratory distress and submucosal cleft palate. All identified patients to-date are compound heterozygotes and each have one missense variant and one frameshift variant. A recurrent missense variant (p.Cys192Tyr) has been identified in 8 individuals from 5 unrelated families. This missense change has been reported as a compound heterozygote with a frameshift variant a patient with seizures and global developmental delay (PMID: 32437232). This variant affects a cysteine residue that is predicted to form a disulphide bond in the protein which is important for protein folding and structural stability. Two recurrent frameshift variants have also been identified: - The p.Gln320ArgfsTer25 variant was found in 3 unrelated individuals (reported as compound heterozyogote in PMID: 32437232). - The p.Ala377ThrfsTer7 variant was found in 5 individuals from 3 unrelated families. CRELD1 encodes a member of a subfamily of epidermal growth factor-related proteins. CRELD1 plays a pivitol role in heart development and has also been shown to be an important gatekeeper of immune system homeostasis (PMID: 33169013). There is one publication that reports a patient with seizures and global developmental delay with biallelic variants in CRELD1 (PMID: 32437232) but no other association between CRELD1 and brain function has been reported to date. Significantly, CRELD1 has high expression in human brain across different developmental stages. There is no phenotype associated with biallelic CRELD1 variants in OMIM or G2P. Sources: Expert Review |
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