Activity
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20 actions
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| Cholestasis v3.14 | RINT1 |
Achchuthan Shanmugasundram Tag Q2_25_ demote_red was removed from gene: RINT1. Tag Q2_25_expert_review was removed from gene: RINT1. |
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| Cholestasis v3.14 | RINT1 | Achchuthan Shanmugasundram edited their review of gene: RINT1: Added comment: The rating of this gene has been updated to red following NHS Genomic Medicine Service approval.; Changed rating: RED | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cholestasis v3.13 | RINT1 |
Achchuthan Shanmugasundram Source NHS GMS was added to RINT1. Source Expert Review Red was added to RINT1. Rating Changed from Green List (high evidence) to Red List (low evidence) |
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| Cholestasis v3.7 | RINT1 |
Achchuthan Shanmugasundram Tag Q2_25_ demote_amber was removed from gene: RINT1. Tag Q2_25_ demote_red tag was added to gene: RINT1. |
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| Cholestasis v3.7 | RINT1 |
Achchuthan Shanmugasundram Tag Q2_25_ demote_red was removed from gene: RINT1. Tag Q2_25_ demote_amber tag was added to gene: RINT1. |
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| Cholestasis v3.7 | RINT1 |
Achchuthan Shanmugasundram Tag Q2_25_ demote_red tag was added to gene: RINT1. Tag Q2_25_expert_review tag was added to gene: RINT1. |
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| Cholestasis v3.7 | RINT1 |
Achchuthan Shanmugasundram changed review comment from: As reviewed previously, PMID:31204009 reported three unrelated individuals with compound heterozygous RINT1 variants and infantile acute liver failure (MIM #618641). However, focal cholestasis was only reported in one patient (proband 3), while jaundice was reported in a different patient (proband 1). Increased bilirubin levels are reported in all three patients. There is also functional evidence on patient dermal fibroblasts available for the splice-variant that was identified in all three patients. PMID:37463447 reported three individuals from two unrelated families with novel biallelic RINT1 loss-of-function variants and they presented with early onset spastic paraplegia, ataxia, optic nerve hypoplasia, dysmorphic features and neurodevelopmental delay, expanding the phenotypic spectrum of the disorder. Although acute liver failure or episodic liver dysfunction are reported in these cases, cholestasis or hyperbilirubinaemia are not reported. PMID:39186236 also reported a patient withy acute liver failure due to RINT1 deficiency, however without any reports of cholestasis or hyperbilirubinaemia. As per the National Genomic Test Directory (https://www.england.nhs.uk/publication/national-genomic-test-directories/), this panel includes both cholestasis and hyperbilirubinaemia. As Zornitza Stark has reviewed this gene red on this panel based on the phenotype being acute liver failure, clinical opinion is sought on whether this gene can remain green on this panel.; to: As reviewed previously, PMID:31204009 reported three unrelated individuals with compound heterozygous RINT1 variants and infantile acute liver failure (MIM #618641). However, focal cholestasis was only reported in one patient (proband 3), while jaundice was reported in a different patient (proband 1). Increased bilirubin levels are reported in all three patients. There is also functional evidence on patient dermal fibroblasts available for the splice-variant that was identified in all three patients. PMID:37463447 reported three individuals from two unrelated families with novel biallelic RINT1 loss-of-function variants and they presented with early onset spastic paraplegia, ataxia, optic nerve hypoplasia, dysmorphic features and neurodevelopmental delay, expanding the phenotypic spectrum of the disorder. Although acute liver failure or episodic liver dysfunction are reported in these cases, cholestasis or hyperbilirubinaemia are not reported. PMID:39186236 also reported a patient withy acute liver failure due to RINT1 deficiency, however without any reports of cholestasis or hyperbilirubinaemia. As per the National Genomic Test Directory (https://www.england.nhs.uk/publication/national-genomic-test-directories/), this panel includes neonatal conjugated hyperbilirubinaemia, unexplained cholestasis or cholestasis of pregnancy-onset. As Zornitza Stark has reviewed this gene red on this panel based on the phenotype being acute liver failure, clinical opinion is sought on whether this gene can remain green on this panel. |
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| Cholestasis v3.7 | RINT1 |
Achchuthan Shanmugasundram changed review comment from: As reviewed previously, PMID:31204009 reported three unrelated individuals with compound heterozygous RNT1 variants and infantile acute liver failure (MIM #618641). However, focal cholestasis was only reported in one patient (proband 3), while jaundice was reported in a different patient (proband 1). Increased bilirubin levels are reported in all three patients. There is also functional evidence on patient dermal fibroblasts available for the splice-variant that was identified in all three patients. PMID:37463447 reported three individuals from two unrelated families with novel biallelic RINT1 loss-of-function variants and they presented with early onset spastic paraplegia, ataxia, optic nerve hypoplasia, dysmorphic features and neurodevelopmental delay, expanding the phenotypic spectrum of the disorder. Although acute liver failure or episodic liver dysfunction are reported in these cases, cholestasis or hyperbilirubinaemia are not reported. PMID:39186236 also reported a patient withy acute liver failure due to RINT1 deficiency, however without any reports of cholestasis or hyperbilirubinaemia. As per the National Genomic Test Directory (https://www.england.nhs.uk/publication/national-genomic-test-directories/), this panel should include both cholestasis and hyperbilirubinaemia. As Zornitza Stark has reviewed this gene red on this panel based on the phenotype being acute liver failure, clinical opinion is sought on whether this gene can remain green on this panel.; to: As reviewed previously, PMID:31204009 reported three unrelated individuals with compound heterozygous RINT1 variants and infantile acute liver failure (MIM #618641). However, focal cholestasis was only reported in one patient (proband 3), while jaundice was reported in a different patient (proband 1). Increased bilirubin levels are reported in all three patients. There is also functional evidence on patient dermal fibroblasts available for the splice-variant that was identified in all three patients. PMID:37463447 reported three individuals from two unrelated families with novel biallelic RINT1 loss-of-function variants and they presented with early onset spastic paraplegia, ataxia, optic nerve hypoplasia, dysmorphic features and neurodevelopmental delay, expanding the phenotypic spectrum of the disorder. Although acute liver failure or episodic liver dysfunction are reported in these cases, cholestasis or hyperbilirubinaemia are not reported. PMID:39186236 also reported a patient withy acute liver failure due to RINT1 deficiency, however without any reports of cholestasis or hyperbilirubinaemia. As per the National Genomic Test Directory (https://www.england.nhs.uk/publication/national-genomic-test-directories/), this panel includes both cholestasis and hyperbilirubinaemia. As Zornitza Stark has reviewed this gene red on this panel based on the phenotype being acute liver failure, clinical opinion is sought on whether this gene can remain green on this panel. |
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| Cholestasis v3.7 | RINT1 | Achchuthan Shanmugasundram reviewed gene: RINT1: Rating: AMBER; Mode of pathogenicity: None; Publications: 31204009, 37463447, 39186236; Phenotypes: Infantile liver failure syndrome 3, OMIM:618641; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cholestasis v3.6 | RINT1 | Zornitza Stark reviewed gene: RINT1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cholestasis v1.105 | RINT1 |
Ivone Leong Tag for-review was removed from gene: RINT1. Tag Q1_22_NHS_review was removed from gene: RINT1. |
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| Cholestasis v1.105 | RINT1 | Ivone Leong commented on gene: RINT1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cholestasis v1.104 | RINT1 |
Ivone Leong Source Expert Review Green was added to RINT1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
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| Cholestasis v1.103 | RINT1 | Ivone Leong Tag Q1_22_NHS_review tag was added to gene: RINT1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cholestasis v1.103 | RINT1 | Miranda Durkie reviewed gene: RINT1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31204009; Phenotypes: Infantile liver failure syndrome 3; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cholestasis v1.78 | RINT1 | Eleanor Williams Classified gene: RINT1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cholestasis v1.78 | RINT1 | Eleanor Williams Added comment: Comment on list classification: Promoting this gene from red to amber, but with recommendation for green rating, pending review of whether the phenotype is within the scope of this panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cholestasis v1.78 | RINT1 | Eleanor Williams Gene: rint1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cholestasis v1.77 | RINT1 | Eleanor Williams Tag for-review tag was added to gene: RINT1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cholestasis v1.77 | RINT1 |
Eleanor Williams gene: RINT1 was added gene: RINT1 was added to Cholestasis. Sources: Literature Mode of inheritance for gene: RINT1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RINT1 were set to 31204009 Phenotypes for gene: RINT1 were set to Infantile liver failure syndrome 3 OMIM:618641; infantile liver failure syndrome 3 MONDO:0032844 Review for gene: RINT1 was set to GREEN Added comment: Associated with Infantile liver failure syndrome 3 #618641 (AR) in OMIM. Probable association with Infantile-Onset Recurrent Acute Liver Failure and Skeletal Abnormalities in Gene2Phenotype. PMID:31204009 - Cousin et al 2019 - describe 3 unrelated children with recurrent acute liver failure (RALF) and skeletal abnormalities who were found by WES to have compound heterozygous alterations in RINT1. All had splice alterations at the same position (c.1333+1G>A or G>T) together with a missense (p.Ala368Thr or p.Leu370Pro) or in-frame deletion (p.Val618_Lys619del). One variant was inherited from each parent. 2 of the 3 children had short stature. Imaging showed that they had abnormalities affecting the vertebrae and pelvis. Studies on patient dermal fibroblasts showed that the splice-variant results in skipping of exon 9 leading to an out-of-frame product and nonsense-mediated transcript decay and that there was decreased RINT1 protein levels, abnormal Golgi morphology, and impaired autophagic flux compared to control fibroblasts. Sources: Literature |
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