Skeletal dysplasia

Gene: RINT1

Green List (high evidence)

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

• 31204009

Green List (high evidence)

Reported in 3 patients with similar phenotype in PMID: 31204009. Caused by one LoF allele and missense/in-frame hypomorphic allele.
Sources: Literature

Created: 14 Oct 2020, 4:26 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
liver failure; short stature; skeletal abnormalities

Publications

• PMID: 31204009

Variants in this GENE are reported as part of current diagnostic practice