Activity
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12 actions
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| Cholestasis v3.12 | UNC45A | Arina Puzriakova Publications for gene: UNC45A were set to 29429573 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cholestasis v3.11 | UNC45A | Arina Puzriakova Phenotypes for gene: UNC45A were changed from Cholestasis; Diarrhoea; Bone fragility; Impaired hearing to Osteootohepatoenteric syndrome, OMIM:619377; Aagenaes syndrome, MONDO:0008966 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cholestasis v3.10 | UNC45A |
Ida Ertmanska changed review comment from: UNC45A has been linked to Aagenaes syndrome - a condition characterized by neonatal cholestasis, lymphedema, and giant cell hepatitis. There are at least 28 affected individuals from 25 different families who presented with neonatal cholestasis and lymphedema (PMIDs:37328071;39887522). Based on the reported evidence, this gene should be rated Green for Cholestasis. PMID: 37328071 Almaas et al., 2023 26 patients with Aagenaes syndrome from 24 different families. 19 individuals homozygous for c.-98G>T (5' UTR region) in UNC45A & 7 individuals compound heterozygous for c.-98G>T (no homozygotes reported in gnomAD v4) and an exonic loss-of-function variant in UNC45A: c.1101delC, p.Lys368Serfs*53; c.1572_1573insAT, p.Asp525Metfs*16; c.1646_1647delTT, p.Phe549Cysfs*37; c.2028+1G>A (intron 18); c.2590C>T, p.Gln864*. Method: WGS + Sanger in first family, Sanger seq in subsequent patients. Tested unaffected parents were heterozygous for either the 5'UTR c.-98G>T variant, or an exonic variant. Phenotype: 26/26 patients presented with cholestasis in infancy and childhood. All patients, except two young infants, had lymphedema of the lower limbs (age of onset: birth - 15 years); 19/26 also had lymphedema of the upper limbs. Confirmed lower expression of UNC45A mRNA and protein in mutant HEK293T cells than controls. Levels of expression of UNC45A mRNA from whole blood (relative to WT controls): 50% for patients homozygous for c.-98G>T; 37% in compound heterozygotes; 79% in parents het for c.-98G>T; 50% in parents het for exonic LoF variants. Similar trend seen in protein levels: 50% of control UNC45A levels in homozygotes, and 17% of control residual blood protein in compound hets. PMID: 39887522 Tan et al., 2025 Two siblings, compound het for c.-88G>A and c.1591C>T, p.(Arg531Ter) in UNC45A. Method: WES Phenotype: both siblings presented with neonatal cholestasis and lymphedema; one sibling developed severe liver failure. This gene is associated with Osteootohepatoenteric syndrome, 619377 in OMIM - hypothesised to be a separate disease entity, characterised by bone fragility, hearing loss, cholestasis, and congenital diarrhea (PMID: 29429573 Esteve et al., 2018).; to: UNC45A has been linked to Aagenaes syndrome - a condition characterized by neonatal cholestasis, lymphedema, and giant cell hepatitis. There are at least 28 affected individuals from 25 different families who presented with neonatal cholestasis and lymphedema (PMIDs:37328071;39887522). Based on the reported evidence, this gene should be rated Green for Cholestasis. PMID: 37328071 Almaas et al., 2023 26 patients with Aagenaes syndrome from 24 different families. 19 individuals homozygous for c.-98G>T (5' UTR region) in UNC45A & 7 individuals compound heterozygous for c.-98G>T (no homozygotes reported in gnomAD v4) and an exonic loss-of-function variant in UNC45A: c.1101delC, p.Lys368Serfs*53; c.1572_1573insAT, p.Asp525Metfs*16; c.1646_1647delTT, p.Phe549Cysfs*37; c.2028+1G>A (intron 18); c.2590C>T, p.Gln864*. Method: WGS + Sanger in first family, Sanger seq in subsequent patients. Tested unaffected parents were heterozygous for either the 5'UTR c.-98G>T variant, or an exonic variant. Phenotype: 26/26 patients presented with cholestasis in infancy and childhood. All patients, except two young infants, had lymphedema of the lower limbs (age of onset: birth - 15 years); 19/26 also had lymphedema of the upper limbs. Confirmed lower expression of UNC45A mRNA and protein in mutant HEK293T cells than controls. Levels of expression of UNC45A mRNA from whole blood (relative to WT controls): 50% for patients homozygous for c.-98G>T; 37% in compound heterozygotes; 79% in parents het for c.-98G>T; 50% in parents het for exonic LoF variants. Similar trend seen in protein levels: 50% of control UNC45A levels in homozygotes, and 17% of control residual blood protein in compound hets. PMID: 39887522 Tan et al., 2025 Two siblings, compound het for c.-88G>A and c.1591C>T, p.(Arg531Ter) in UNC45A. Method: WES Phenotype: both siblings presented with neonatal cholestasis and lymphedema; one sibling developed severe liver failure. This gene is associated with Osteootohepatoenteric syndrome, 619377 in OMIM (accessed 10th Oct 2025) - hypothesised to be a separate disease entity, characterised by bone fragility, hearing loss, cholestasis, and congenital diarrhea (PMID: 29429573 Esteve et al., 2018). |
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| Cholestasis v3.10 | UNC45A | Ida Ertmanska reviewed gene: UNC45A: Rating: GREEN; Mode of pathogenicity: None; Publications: 37328071, 39887522; Phenotypes: Osteootohepatoenteric syndrome, OMIM:619377, Aagenaes syndrome, MONDO:0008966; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cholestasis v1.105 | UNC45A | Ivone Leong Tag for-review was removed from gene: UNC45A. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cholestasis v1.105 | UNC45A | Ivone Leong commented on gene: UNC45A: The rating of this gene has been updated following NHS Genomic Medicine Service approval. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cholestasis v1.104 | UNC45A |
Ivone Leong Source Expert Review Green was added to UNC45A. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
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| Cholestasis v1.36 | UNC45A | Ivone Leong Classified gene: UNC45A as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cholestasis v1.36 | UNC45A | Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark. There is enough evidence to support a gene-disease association. This gene has been given an Amber rating and will be promoted to Green at the next panel review. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cholestasis v1.36 | UNC45A | Ivone Leong Gene: unc45a has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cholestasis v1.35 | UNC45A | Ivone Leong Tag for-review tag was added to gene: UNC45A. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cholestasis v1.16 | UNC45A |
Zornitza Stark gene: UNC45A was added gene: UNC45A was added to Cholestasis. Sources: Expert list Mode of inheritance for gene: UNC45A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: UNC45A were set to 29429573 Phenotypes for gene: UNC45A were set to Cholestasis; Diarrhoea; Bone fragility; Impaired hearing Review for gene: UNC45A was set to GREEN gene: UNC45A was marked as current diagnostic Added comment: Three unrelated families reported. Sources: Expert list |
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