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Ichthyosis and erythrokeratoderma v3.19 | SASH1 | Arina Puzriakova Phenotypes for gene: SASH1 were changed from Pigmentation defects, palmoplantar keratoderma and skin carcinoma to ?Cancer, alopecia, pigment dyscrasia, onychodystrophy, and keratoderma, OMIM:618373 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Ichthyosis and erythrokeratoderma v3.17 | FAM83G | Arina Puzriakova Added comment: Comment on list classification: Upgraded rating from Red to Amber inline with expert review by Tom Cullup (GOSH) to facilitate further gathering of data where appropriate which could potentially support future promotion to Green. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Ichthyosis and erythrokeratoderma v3.3 | DBR1 |
Zornitza Stark gene: DBR1 was added gene: DBR1 was added to Ichthyosis and erythrokeratoderma. Sources: Literature Mode of inheritance for gene: DBR1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DBR1 were set to 37656279 Phenotypes for gene: DBR1 were set to Ichthyosis (MONDO#0019269), DBR1-related Review for gene: DBR1 was set to AMBER Added comment: PMID: 37656279: - A homozygous missense as a founder recessive DBR1 variant in four consanguineous families. - Total of 7 affected children. WES done for one proband from each family. - Consistent features include prematurity, severe intrauterine growth deficiency, congenital ichthyosis-like presentation (collodion membrane, severe skin peeling and xerosis), and death before the first year of life. - RNA and protein studies using fibroblasts derived from a patient are supportive of pathogenicity: RNA-seq, rt-qPCR and western blotting, showing marked reduction of DBR1 level and intronic RNA lariat accumulation in the patient sample. - Haplotype analysis revealed that the four families all share a haplotype extending at least 2.27 Mb around the c.200A>G p.(Tyr67Cys) DBR1 founder variant. - Authors proposed this is a novel DBR1-related developmental disorder that is distinct from DBR1-related encephalitis susceptibility, and highlighted the apparent lack of correlation with the degree of DBR1 deficiency. Sources: Literature |
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Ichthyosis and erythrokeratoderma v2.12 | GJA1 | Arina Puzriakova commented on gene: GJA1: The mode of inheritance of this gene has been updated to 'MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown' following NHS Genomic Medicine Service approval. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Ichthyosis and erythrokeratoderma v2.11 | GJA1 |
Arina Puzriakova Source NHS GMS was added to GJA1. Mode of inheritance for gene GJA1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown |
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Ichthyosis and erythrokeratoderma v1.60 | ALDH1L2 |
Zornitza Stark gene: ALDH1L2 was added gene: ALDH1L2 was added to Ichthyosis and erythrokeratoderma. Sources: Literature Mode of inheritance for gene: ALDH1L2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ALDH1L2 were set to 31341639; 33168096 Phenotypes for gene: ALDH1L2 were set to pruritic ichthyosis, severe diffuse hypomyelination seen on MRI, and abnormal lipid peaks Review for gene: ALDH1L2 was set to RED Added comment: Individual reported with bialleleic ALDH1L2 variants (non-canonical splice and a frameshift mutation), who also has a de novo hemizygous RPS6KA3 frameshift mutation. Authors state that not all features of the individual could be explained by the RPS6KA3 variant, and that consideration of Coffin-Lowry sysndrome was only made after identification of the RPS6KA3 variant. Therefore individual has there is a blended phenotype of Coffin–Lowry syndrome and Sjögren–Larsson syndrome. From functional studies authors propose that the ALDH1L2 loss induces mitochondrial dysfunction due to reduced NADPH and increased oxidative stress (PMID: 31341639). Knockout mouse model was viable and did not show an apparent phenotype, however metabolomic analysis showed vastly changed metabotypes in the liver and plasma in these mice suggesting channeling of fatty acids away from β-oxidation. Authors therefore postulate that the role of ALDH1L2 in the lipid metabolism explains why the loss of this enzyme is associated with neuro-cutaneous disease. Sources: Literature |
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Ichthyosis and erythrokeratoderma v1.56 | TAT |
Ivone Leong Added comment: Comment on phenotypes: Previous phenotypes: palmoplantar hyperkeratosis;KERATOSIS PALMOPLANTARIS WITH CORNEAL DYSTROPHY;Tyrosinemia, type II, 276600 |
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Ichthyosis and erythrokeratoderma v1.56 | TAT | Ivone Leong Phenotypes for gene: TAT were changed from palmoplantar hyperkeratosis; KERATOSIS PALMOPLANTARIS WITH CORNEAL DYSTROPHY; Tyrosinemia, type II, 276600 to Tyrosinemia, type II, OMIM:276600 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Ichthyosis and erythrokeratoderma v1.23 | ENPP1 | Ivone Leong Phenotypes for gene: ENPP1 were changed from Cole disease, 615522 (includes punctate palmoplantar keratoderma) to Cole disease, OMIM:615522 (includes punctate palmoplantar keratoderma) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Ichthyosis and erythrokeratoderma v1.15 | CAST | Ivone Leong Phenotypes for gene: CAST were changed from Peeling skin with leukonychia, acral punctate keratoses, cheilitis, and knuckle pads 616295 to Peeling skin with leukonychia, acral punctate keratoses, cheilitis, and knuckle pads, OMIM:616295 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Ichthyosis and erythrokeratoderma v1.7 | AAGAB |
Ivone Leong Added comment: Comment on phenotypes: Previous phenotypes: Keratoderma, palmoplantar, punctate type IA, 148600;PPKP Buschke-Fischer-Brauer type;Punctate keratoderma and congenital dysplasia of the hip;Punctate keratoderma |
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Ichthyosis and erythrokeratoderma v1.7 | AAGAB | Ivone Leong Phenotypes for gene: AAGAB were changed from Keratoderma, palmoplantar, punctate type IA, 148600; PPKP Buschke-Fischer-Brauer type; Punctate keratoderma and congenital dysplasia of the hip; Punctate keratoderma to Keratoderma, palmoplantar, punctate type IA, OMIM:148600; PPKP Buschke-Fischer-Brauer type; Punctate keratoderma and congenital dysplasia of the hip | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Ichthyosis and erythrokeratoderma v1.3 | PERP |
Zornitza Stark gene: PERP was added gene: PERP was added to Ichthyosis and erythrokeratoderma. Sources: Literature Mode of inheritance for gene: PERP was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PERP were set to 31898316 Phenotypes for gene: PERP were set to Erythrokeratoderma, no OMIM # yet Review for gene: PERP was set to AMBER Added comment: One extended multiplex consanguineous family with Erythrokeratoderma (striking similarity to that observed in Perp −/− mice), and a novel homozygous variant (c.466G>A; p.Gly156Arg) in PERP that fully segregated with the phenotype. Functional analysis of patient‐ and control‐derived keratinocytes revealed a deleterious effect of the identified variant on the intracellular localization of PERP. A previous report showed that PERP mutation causes a dominant form of keratoderma but a single patient in that report with a homozygous variant in PERP suggests that recessive inheritance is also possible. Sources: Literature |
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Ichthyosis and erythrokeratoderma v0.9 | FLG |
Catherine Snow gene: FLG was added gene: FLG was added to Ichthyosis and erythrokeratoderma. Sources: Expert Review Amber Mode of inheritance for gene: FLG was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown |
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Ichthyosis and erythrokeratoderma v0.9 | LOR |
Catherine Snow gene: LOR was added gene: LOR was added to Ichthyosis and erythrokeratoderma. Sources: Expert Review Amber Mode of inheritance for gene: LOR was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown |
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Ichthyosis and erythrokeratoderma v0.9 | KRT2 |
Catherine Snow gene: KRT2 was added gene: KRT2 was added to Ichthyosis and erythrokeratoderma. Sources: Expert Review Amber Mode of inheritance for gene: KRT2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown |
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Ichthyosis and erythrokeratoderma v0.3 | TAT |
Ellen McDonagh gene: TAT was added gene: TAT was added to Ichthyosis and erythrokeratoderma. Sources: Expert Review Green Mode of inheritance for gene: TAT was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: TAT were set to palmoplantar hyperkeratosis; KERATOSIS PALMOPLANTARIS WITH CORNEAL DYSTROPHY; Tyrosinemia, type II, 276600 |
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Ichthyosis and erythrokeratoderma v0.3 | STS |
Ellen McDonagh gene: STS was added gene: STS was added to Ichthyosis and erythrokeratoderma. Sources: Expert Review Green Mode of inheritance for gene: STS was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Phenotypes for gene: STS were set to Ichthyosis, X-linked, 308100 |
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Ichthyosis and erythrokeratoderma v0.3 | SMARCAD1 |
Ellen McDonagh gene: SMARCAD1 was added gene: SMARCAD1 was added to Ichthyosis and erythrokeratoderma. Sources: Expert Review Amber Mode of inheritance for gene: SMARCAD1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: SMARCAD1 were set to 24909267; 26932190; 24664640 Phenotypes for gene: SMARCAD1 were set to Basan syndrome, 129200; palmoplantar keratoderma |
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Ichthyosis and erythrokeratoderma v0.3 | SLURP1 |
Ellen McDonagh gene: SLURP1 was added gene: SLURP1 was added to Ichthyosis and erythrokeratoderma. Sources: Expert Review Green Mode of inheritance for gene: SLURP1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Publications for gene: SLURP1 were set to 16865292; 24738704; 14756676; 9887370; 25557416; 12483299; 24985918; 19692209; 17184264; 24604124; 16882192; 15026760; 11285253; 21690549; 23290002; 19120323 Phenotypes for gene: SLURP1 were set to keratosis palmoplantaris transgrediens; Diffuse palmoplantar keratoderma; palmoplantar keratoderma; Mal de Meleda (MDM); Meleda disease, 248300 |
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Ichthyosis and erythrokeratoderma v0.3 | SASH1 |
Ellen McDonagh gene: SASH1 was added gene: SASH1 was added to Ichthyosis and erythrokeratoderma. Sources: Expert Review Red Mode of inheritance for gene: SASH1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SASH1 were set to 25315659 Phenotypes for gene: SASH1 were set to Pigmentation defects, palmoplantar keratoderma and skin carcinoma |
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Ichthyosis and erythrokeratoderma v0.3 | MBTPS2 |
Ellen McDonagh gene: MBTPS2 was added gene: MBTPS2 was added to Ichthyosis and erythrokeratoderma. Sources: Expert Review Red Mode of inheritance for gene: MBTPS2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: MBTPS2 were set to 22931912; 24313295 Phenotypes for gene: MBTPS2 were set to X-linked mutilating palmoplantar keratoderma with periorificial keratotic plaques (Olmsted syndrome); ?Olmsted syndrome, X-linked, 300918; IFAP syndrome. 308205, along with pachyonychia, palmoplantar and periorificial keratoderma |
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Ichthyosis and erythrokeratoderma v0.3 | KRT17 |
Ellen McDonagh gene: KRT17 was added gene: KRT17 was added to Ichthyosis and erythrokeratoderma. Sources: Expert Review Green Mode of inheritance for gene: KRT17 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Publications for gene: KRT17 were set to 15102078; 22336949; 9008238; 7539673; 19659471 Phenotypes for gene: KRT17 were set to Steatocystoma multiplex, 184500; Pachyonychia congenita, Jackson-Lawler type, 167210; Pachyonychia Congenita, Type 2 |
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Ichthyosis and erythrokeratoderma v0.3 | ISCA-37417-Loss |
Ellen McDonagh Region: ISCA-37417-Loss was added Region: ISCA-37417-Loss was added to Ichthyosis and erythrokeratoderma. Sources: Expert Review Green Mode of inheritance for Region: ISCA-37417-Loss was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for Region: ISCA-37417-Loss were set to 308100; Ichthyosis, X-linked |
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Ichthyosis and erythrokeratoderma v0.3 | ENPP1 |
Ellen McDonagh gene: ENPP1 was added gene: ENPP1 was added to Ichthyosis and erythrokeratoderma. Sources: Expert Review Green Mode of inheritance for gene: ENPP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ENPP1 were set to 26617416; 24075184; 19380683 Phenotypes for gene: ENPP1 were set to Cole disease, 615522 (includes punctate palmoplantar keratoderma) |
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Ichthyosis and erythrokeratoderma v0.3 | ELOVL4 |
Ellen McDonagh gene: ELOVL4 was added gene: ELOVL4 was added to Ichthyosis and erythrokeratoderma. Sources: Expert Review Red Mode of inheritance for gene: ELOVL4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: ELOVL4 were set to 24566826; 26010696 Phenotypes for gene: ELOVL4 were set to Spinocerebellar ataxia 34 133190 |
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Ichthyosis and erythrokeratoderma v0.3 | DSP |
Ellen McDonagh gene: DSP was added gene: DSP was added to Ichthyosis and erythrokeratoderma. Sources: Expert Review Green Mode of inheritance for gene: DSP was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Publications for gene: DSP were set to 22795705; 11841538; 16628197; 19924139; 11063735; 20940358; 26303123; 10594734; 20738328; 16175511; 25516398 Phenotypes for gene: DSP were set to Skin fragility-woolly hair syndrome; Keratosis palmoplantaris striata II, 612908; lethal acantholytic epidermolysis bullosa, 609638; Striate keratoderma with woolly hair and cardiomyopathy; Skin fragility-woolly hair syndrome, 607655; oligodontia or hypodontia; alopecia, follicular hyperkeratoses and keratoderma; diffuse keratoderma; Epidermolysis bullosa, lethal acantholytic; striate keratoderma; CARVAJAL SYNDROME; Arrhythmogenic right ventricular dysplasia 8, 607450; Keratosis palmoplantaris striata II; Dilated cardiomyopathy with woolly hair and keratoderma, 605676 |
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Ichthyosis and erythrokeratoderma v0.3 | DSG2 |
Ellen McDonagh gene: DSG2 was added gene: DSG2 was added to Ichthyosis and erythrokeratoderma. Sources: Expert Review Red Mode of inheritance for gene: DSG2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: DSG2 were set to Arrhythmogenic right ventricular dysplasia 10 Cardiomyopathy, dilated, 1BB; Striate keratoderma with woolly hair |
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Ichthyosis and erythrokeratoderma v0.3 | DES |
Ellen McDonagh gene: DES was added gene: DES was added to Ichthyosis and erythrokeratoderma. Sources: Expert Review Red Mode of inheritance for gene: DES was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: DES were set to Striate keratoderma with woolly hair; Cardiomyopathy, dilated, 1I |
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Ichthyosis and erythrokeratoderma v0.3 | CAST |
Ellen McDonagh gene: CAST was added gene: CAST was added to Ichthyosis and erythrokeratoderma. Sources: Expert Review Green Mode of inheritance for gene: CAST was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: CAST were set to Peeling skin with leukonychia, acral punctate keratoses, cheilitis, and knuckle pads 616295 |
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Ichthyosis and erythrokeratoderma v0.3 | AAGAB |
Ellen McDonagh gene: AAGAB was added gene: AAGAB was added to Ichthyosis and erythrokeratoderma. Sources: Expert Review Green Mode of inheritance for gene: AAGAB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: AAGAB were set to 23563198; 24289292; 23000146; 23064416 Phenotypes for gene: AAGAB were set to Keratoderma, palmoplantar, punctate type IA, 148600; PPKP Buschke-Fischer-Brauer type; Punctate keratoderma and congenital dysplasia of the hip; Punctate keratoderma |