Intellectual disability
Gene: ITSN1
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, 2:11 p.m. | Last Modified: 11 Jun 2024, 2:11 p.m.
Panel Version: 6.21
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, 2:10 p.m. | Last Modified: 11 Jun 2024, 2:10 p.m.
Panel Version: 6.21
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, 2:10 p.m. | Last Modified: 11 Jun 2024, 2:10 p.m.
Panel Version: 6.21
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, 2:09 p.m. | Last Modified: 11 Jun 2024, 2:09 p.m.
Panel Version: 6.21
Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS updateCreated: 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
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: LiteratureCreated: 6 Jun 2024, 9:32 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
autism spectrum disorders; intellectual disability; epilepsy.
Publications
Variants in this GENE are reported as part of current diagnostic practice
Gene: itsn1 has been classified as Amber List (Moderate Evidence).
Gene: itsn1 has been classified as Amber List (Moderate Evidence).
Gene: itsn1 has been classified as Amber List (Moderate Evidence).
Gene: itsn1 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: ITSN1 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Gene: itsn1 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: ITSN1 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Phenotypes for gene: ITSN1 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Phenotypes for gene: ITSN1 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Phenotypes for gene: ITSN1 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Phenotypes for gene: ITSN1 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Phenotypes for gene: ITSN1 were changed from autism spectrum disorders; intellectual disability; epilepsy. to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Publications for gene: ITSN1 were set to Bruel et al., 2021 (PMID: 34707297):
Tag Q2_24_promote_green tag was added to gene: ITSN1. Tag Q2_24_NHS_review tag was added to gene: ITSN1.
gene: ITSN1 was added gene: ITSN1 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: ITSN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ITSN1 were set to Bruel et al., 2021 (PMID: 34707297): Phenotypes for gene: ITSN1 were set to autism spectrum disorders; intellectual disability; epilepsy. Penetrance for gene: ITSN1 were set to unknown Review for gene: ITSN1 was set to GREEN gene: ITSN1 was marked as current diagnostic