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| Ichthyosis and Porokeratosis v2.3 | ERO1A |
chirag patel gene: ERO1A was added gene: ERO1A was added to Ichthyosis and Porokeratosis. Sources: Other Mode of inheritance for gene: ERO1A was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: ERO1A were set to Ichthyosis, keratoderma and bone fragility Review for gene: ERO1A was set to AMBER Added comment: ESHG 2026 3 individuals from 2 unrelated families (1 consanguineous) with homozygous variants in ERO1A ((p.His22Glnfs19) and p.(Gln154*)). They presented with ichthyosis (3), palmoplantar keratoderma (3), sparse eyebrows (2), fragile nails (2), microcephaly (2), low bone mineral density (1), and recurrent long bone fractures in early childhood (2). The variants segregated in the families. Endoplasmic reticulum (ER) oxidoreductase 1α (ERO1A) oxidizes the protein disulfide isomerase (PDI) and promotes disulfide bond formation in newly synthesized polypeptides such as collagen I. The 3 patient-derived fibroblasts showed significantly reduced ERO1A mRNA levels, indicating nonsense-mediated mRNA decay. This was accompanied by absence of ERO1A protein and increased PDI levels. In whole-cell lysates from fibroblasts of 2 patients, collagen I was detected as a triple band, whereas only two bands were observed in control cells. They found disordered collagen I aggregates in the extracellular matrix of all patient-derived fibroblasts. As a possible compensatory response, mRNA and protein levels for the collagen-specific ER chaperone HSP47 were increased in patient cells. Sources: Other |
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| Ichthyosis and Porokeratosis v2.0 | STS | Gene migrated from ENSG00000101846 to ENSG00000101846 (gene set migration) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ichthyosis and Porokeratosis v1.5 | DBR1 |
Chern Lim edited their review of gene: DBR1: 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.; Changed phenotypes: Ichthyosis (MONDO#0019269), DBR1-related |
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| Ichthyosis and Porokeratosis v1.4 | DBR1 |
Chern Lim gene: DBR1 was added gene: DBR1 was added to Ichthyosis. 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 Prematurity, severe intrauterine growth deficiency, congenital ichthyosis-like presentation, and death before the first year of life Review for gene: DBR1 was set to AMBER gene: DBR1 was marked as current diagnostic Added comment: PMID: 37656279: - A homozygous missense as a founder recessive DBR1 variant in four consanguineous families. - 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 Porokeratosis v1.3 | PRSS8 |
Lucy Spencer gene: PRSS8 was added gene: PRSS8 was added to Ichthyosis. Sources: Literature Mode of inheritance for gene: PRSS8 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PRSS8 were set to 36715754 Phenotypes for gene: PRSS8 were set to ichthyosis MONDO:0019269, PRSS8-related Review for gene: PRSS8 was set to AMBER Added comment: PMID: 36715754 1 family with 3 affected sons with congenital ichthyosis, consanguineous parents. All 3 affected members are homozygous for a canonical splice in PRSS8, quantitative RT-PCR showed a significant reduction in normal PRSS8 transcript. A second family with 4 affected members (proband and 3 cousins) with ichthyosis (3 also had autism), also consanguineous. Only the proband was tested who is homozygous for a missense in PTSS8. However this patient also had a TAAR1 missense (no disease association, but the paper suggests this could be responsible for the autism phenotype- KO mice have abnormal learning behaviour). Sources: Literature |
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| Ichthyosis and Porokeratosis v0.120 | STS | Zornitza Stark edited their review of gene: STS: Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ichthyosis and Porokeratosis v0.120 | STS | Zornitza Stark Marked gene: STS as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ichthyosis and Porokeratosis v0.120 | STS | Zornitza Stark Gene: sts has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ichthyosis and Porokeratosis v0.120 | STS | Zornitza Stark Phenotypes for gene: STS were changed from to Ichthyosis, X-linked, MIM# 308100 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ichthyosis and Porokeratosis v0.119 | STS | Zornitza Stark Mode of inheritance for gene: STS was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ichthyosis and Porokeratosis v0.118 | STS | Zornitza Stark Tag SV/CNV tag was added to gene: STS. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ichthyosis and Porokeratosis v0.118 | STS | Zornitza Stark reviewed gene: STS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ichthyosis, X-linked, MIM# 308100; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ichthyosis and Porokeratosis v0.79 | ASPRV1 |
Ee Ming Wong gene: ASPRV1 was added gene: ASPRV1 was added to Ichthyosis. Sources: Literature Mode of inheritance for gene: ASPRV1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ASPRV1 were set to PMID: 32516568 Phenotypes for gene: ASPRV1 were set to palmoplantar keratoderma; lamellar ichthyosis Review for gene: ASPRV1 was set to GREEN gene: ASPRV1 was marked as current diagnostic Added comment: -3 heterozygous missense variants identified across 4 unrelated kindreds -mutant ASPRV1 expressed in human keratinocytes suggests impaired filaggrin processing Sources: Literature |
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| Ichthyosis and Porokeratosis v0.0 | STS |
Zornitza Stark gene: STS was added gene: STS was added to Ichthyosis_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: STS was set to Unknown |
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