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.
Created: 27 Jan 2021, 4:45 p.m. | Last Modified: 27 Jan 2021, 4:45 p.m.
Panel Version: 1.78
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: 27 Jan 2021, 4:44 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Infantile liver failure syndrome 3 OMIM:618641; infantile liver failure syndrome 3 MONDO:0032844
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 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