Intellectual disability
Gene: ITSN1

ITSN1 (intersectin 1)
EnsemblGeneIds (GRCh38): ENSG00000205726
EnsemblGeneIds (GRCh37): ENSG00000205726
OMIM: 602442, Gene2Phenotype
ITSN1 is in 2 panels

2 reviews

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval.
Created: 26 Sep 2024, 2:57 p.m. | Last Modified: 26 Sep 2024, 2:57 p.m.

Panel Version: 7.41

Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS update
Created: 11 Jun 2024, 2:08 p.m. | Last Modified: 11 Jun 2024, 2:08 p.m.

Panel Version: 6.21

As reviewed by John Taylor, PMID:34707297 reported 10 individuals from eight unrelated families with an autosomal dominant neurodevelopmental disorder and with monoallelic ITSN1 variants. All of them had global developmental delay, while intellectual disability was reported in five of these individuals (mild in four and mild-moderate in one).

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Created: 11 Jun 2024, 2:02 p.m. | Last Modified: 11 Jun 2024, 2:02 p.m.

Panel Version: 6.18

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071

Publications

34707297

Created: 11 Jun 2024, 2:02 p.m.
Last Modified: 11 Jun 2024, 2:02 p.m.
Panel version: 7.41

John Taylor (Oxford Medical Genetics Laboratory)

Green List (high evidence)

Bruel et al 2021 (PMID: 34707297):
Recent studies in large cohorts of subjects with neurodevelopmental disorders have identified de novo variants in ITSN1 gene thereby suggesting that this gene is involved in the development of such disorders.

A worldwide collaboration identified ten novel patients from eight families with heterozygous truncating or missense variants in ITSN1 gene. All patients underwent detailed phenotypic and genetic assessment and data was collected and shared by healthcare givers.

In addition, four previously published patients from large meta-analysis studies were included.
In total, 7/14 patients presented a de novo variant in ITSN1. Frameshift, nonsense and splice site variants would be consistent with haploinsufficiency. gnomADv4.1 indicates the ITSN1 gene is intolerant to LoF variants and Decipher indicates a high haploinsufficiency index score.

All patients showed neurodevelopmental disorders from autism spectrum disorders (90%), intellectual disability (86%), and epilepsy (30%). Minor and inconstant dysmorphic features were observed. Gastro-intestinal problems including constipation, diarrhoea, and gastroesophageal reflux was reported in some patients. Intellectual disability (IQ test) was reported to range from mild to moderate. In two families, the ITSN1 variant was inherited from a paucisymptomatic father, who were reported to present with ADHD, or learning difficulties and autistic features. Patients 8,9, and 10 (Bruel et al., 2021) inherited the familial nonsense variant from their father (learning difficulties and autistic features) and one unaffected sibling was not found to have the variant.
Sources: Literature
Created: 6 Jun 2024, 9:32 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
autism spectrum disorders; intellectual disability; epilepsy.

Publications

Bruel et al., 2021 (PMID: 34707297):

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

Created: 6 Jun 2024, 9:32 a.m.

Panel version: 6.16

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Sources

Expert Review Green
NHS GMS

Phenotypes

neurodevelopmental disorder, MONDO:0700092
intellectual disability, MONDO:0001071

Tags

gene-checked

OMIM

602442

Clinvar variants

Variants in ITSN1

Penetrance

unknown

Publications

34707297

Panels with this gene

History Filter Activity

2 Oct 2024, Gel status: 3

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag gene-checked tag was added to gene: ITSN1.

26 Sep 2024, Gel status: 3