Skeletal dysplasia
Gene: RINT1
The rating of this gene has been updated following NHS Genomic Medicine Service approval.Created: 6 Mar 2022, 5:41 p.m. | Last Modified: 6 Mar 2022, 5:41 p.m.
Panel Version: 2.176
Comment on list classification: Promoting this gene from grey to amber, but with a recommendation for a green rating following GMS review. 3 cases with compound het variants in this gene.Created: 20 Jan 2021, 11:14 a.m. | Last Modified: 20 Jan 2021, 11:14 a.m.
Panel Version: 2.48
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.Created: 20 Jan 2021, 11:11 a.m. | Last Modified: 27 Jan 2021, 4:24 p.m.
Panel Version: 2.76
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Infantile liver failure syndrome 3 OMIM:618641; infantile liver failure syndrome 3 MONDO:0032844
Publications
Reported in 3 patients with similar phenotype in PMID: 31204009. Caused by one LoF allele and missense/in-frame hypomorphic allele.
Sources: LiteratureCreated: 14 Oct 2020, 4:26 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
liver failure; short stature; skeletal abnormalities
Publications
Variants in this GENE are reported as part of current diagnostic practice
Tag for-review was removed from gene: RINT1.
Source Expert Review Green was added to RINT1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Phenotypes for gene: RINT1 were changed from liver failure; short stature; skeletal abnormalities to liver failure; short stature; skeletal abnormalities; Infantile liver failure syndrome 3 OMIM:618641; infantile liver failure syndrome 3 MONDO:0032844
Publications for gene: RINT1 were set to PMID: 31204009
Gene: rint1 has been classified as Amber List (Moderate Evidence).
Tag for-review tag was added to gene: RINT1.
gene: RINT1 was added gene: RINT1 was added to Skeletal dysplasia. Sources: Literature Mode of inheritance for gene: RINT1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RINT1 were set to PMID: 31204009 Phenotypes for gene: RINT1 were set to liver failure; short stature; skeletal abnormalities Penetrance for gene: RINT1 were set to Complete Review for gene: RINT1 was set to GREEN gene: RINT1 was marked as current diagnostic