Intellectual disability - microarray and sequencing
Gene: ROBO1
The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.Created: 11 Oct 2023, 9:34 a.m. | Last Modified: 11 Oct 2023, 9:34 a.m.
Panel Version: 5.286
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Comment on gene classification: This gene should be rated green as this gene has been associated with intellectual disability from six unrelated cases. However, the MOI should be set as "BIALLELIC, autosomal or pseudoautosomal" as five of these cases were reported with biallelic variants and only one case was reported with monoallelic variant.
PMID:28286008 reported a boy with compound heterozygous variants that was presented with developmental delay in 13 months and had severe intellectual disability and hyperactivity at nine years of age. He was nonverbal and wheelchair dependent because of spastic diplegia and ataxia.
PMID:30692597 reported a five year old boy identified with a homozygous ROBO1 variant who had combined pituitary hormone deficiency, psychomotor developmental delay, severe intellectual disability, sensorineural hearing loss, strabismus and characteristic facial features.
PMID:35227688 reported eight patients including the boy reported in PMID:30692597. Of the other seven patients, three were presented with intellectual disability. Of these three patients, two harboured compound heterozygous and one harboured homozygous variants.
PMID:35348658 reported a patient identified with monoallelic de novo variant (p.D422G) who presented with early-onset epileptic encephalopathy and had severe developmental delay.
This gene has not yet been associated with any phenotypes in OMIM or Gene2Phenotype.Created: 22 Feb 2023, 4:34 p.m. | Last Modified: 22 Feb 2023, 4:43 p.m.
Panel Version: 4.72
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
intellectual disability, MONDO:0001071
Publications
DD/ID has been reported in some individuals with biallelic (e.g. 4 subjects in the study by Münch et al, 1 additional case reported by Calloni et al) or monoallelic ROBO1 variants (e.g. P2 in the study by Huang et al, with a diagnosis of EOEE due to a neomorphic variant).
Consider amber rating pending further review.
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Huang et al (2022 - PMID: 35348658) Monoallelic & Biallelic
Novel dominant and recessive variants in human ROBO1 cause distinct neurodevelopmental defects through different mechanisms.
Münch et al (2022 - PMID: 35227688) Biallelic
Biallelic pathogenic variants in roundabout guidance receptor 1 associate with syndromic congenital anomalies of the kidney and urinary tract
Woodring et al (2021 - PMID: 34193621) - Probably not relevant (VUS)
Uncertain, Not Unimportant: Callosal Dysgenesis and Variants of Uncertain Significance in ROBO1
Liu et al (2020 - PMID: 31448886) Monoallelic
A Novel Missense Mutation in Human Receptor Roundabout-1 (ROBO1) Gene Associated with Pituitary Stalk Interruption Syndrome.
Dateki et al (2019 - PMID: 30692597) Biallelic - This individual has been incl. in the study by Munch et al
A homozygous splice site ROBO1 mutation in a patient with a novel syndrome with combined pituitary hormone deficiency
Rasmussen et al (2018 - PMID: 29194579) Biallelic
Targeted gene sequencing and whole-exome sequencing in autopsied fetuses with prenatally diagnosed kidney anomalies
Kruszka et al (2017 - PMID: 28592524) Monoallelic
Loss of function in ROBO1 is associated with tetralogy of Fallot and septal defects
Bashamboo et al (2017 - PMID: 28402530) Monoallelic
Mutations in the Human ROBO1 Gene in Pituitary Stalk Interruption Syndrome
Calloni et al (2017 - PMID: 28286008) Biallelic
Compound Heterozygous Variants in ROBO1 Cause a Neurodevelopmental Disorder With Absence of Transverse Pontine Fibers and Thinning of the Anterior Commissure and Corpus Callosum
Sources: LiteratureCreated: 11 May 2022, 6:07 a.m.
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
ROBO1-related NDD
Publications
Tag watchlist_moi tag was added to gene: ROBO1.
Phenotypes for gene: ROBO1 were changed from ROBO1-related NDD; intellectual disability, MONDO:0001071 to Intellectual disability, MONDO:0001071; Neurooculorenal syndrome, OMIM:620305
Tag Q1_23_promote_green was removed from gene: ROBO1.
Source NHS GMS was added to ROBO1. Source Expert Review Green was added to ROBO1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Phenotypes for gene: ROBO1 were changed from ROBO1-related NDD; intellectual disability, MONDO:0001071 to ROBO1-related NDD; intellectual disability, MONDO:0001071
Phenotypes for gene: ROBO1 were changed from ROBO1-related NDD; intellectual disability, MONDO:0001071 to ROBO1-related NDD; intellectual disability, MONDO:0001071
Tag Q1_23_promote_green tag was added to gene: ROBO1.
Phenotypes for gene: ROBO1 were changed from ROBO1-related NDD; intellectual disability, MONDO:0001071 to ROBO1-related NDD; intellectual disability, MONDO:0001071
Phenotypes for gene: ROBO1 were changed from ROBO1-related NDD; intellectual disability, MONDO:0001071 to ROBO1-related NDD; intellectual disability, MONDO:0001071
Phenotypes for gene: ROBO1 were changed from ROBO1-related NDD; intellectual disability, MONDO:0001071 to ROBO1-related NDD; intellectual disability, MONDO:0001071
Phenotypes for gene: ROBO1 were changed from ROBO1-related NDD; intellectual disability, MONDO:0001071 to ROBO1-related NDD; intellectual disability, MONDO:0001071
Phenotypes for gene: ROBO1 were changed from ROBO1-related NDD; intellectual disability, MONDO:0001071 to ROBO1-related NDD; intellectual disability, MONDO:0001071
Phenotypes for gene: ROBO1 were changed from ROBO1-related NDD; intellectual disability, MONDO:0001071 to ROBO1-related NDD; intellectual disability, MONDO:0001071
Phenotypes for gene: ROBO1 were changed from ROBO1-related NDD; intellectual disability, MONDO:0001071 to ROBO1-related NDD; intellectual disability, MONDO:0001071
Phenotypes for gene: ROBO1 were changed from ROBO1-related NDD; intellectual disability, MONDO:0001071 to ROBO1-related NDD; intellectual disability, MONDO:0001071
Mode of inheritance for gene: ROBO1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mode of inheritance for gene: ROBO1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ROBO1 were changed from ROBO1-related NDD to ROBO1-related NDD; intellectual disability, MONDO:0001071
Mode of inheritance for gene: ROBO1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mode of inheritance for gene: ROBO1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mode of inheritance for gene: ROBO1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mode of inheritance for gene: ROBO1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mode of inheritance for gene: ROBO1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mode of inheritance for gene: ROBO1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mode of inheritance for gene: ROBO1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mode of inheritance for gene: ROBO1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Gene: robo1 has been classified as Amber List (Moderate Evidence).
Mode of inheritance for gene: ROBO1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Gene: robo1 has been classified as Amber List (Moderate Evidence).
Mode of inheritance for gene: ROBO1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mode of inheritance for gene: ROBO1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mode of inheritance for gene: ROBO1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Gene: robo1 has been classified as Amber List (Moderate Evidence).
Gene: robo1 has been classified as Amber List (Moderate Evidence).
Gene: robo1 has been classified as Amber List (Moderate Evidence).
Gene: robo1 has been classified as Amber List (Moderate Evidence).
gene: ROBO1 was added gene: ROBO1 was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: ROBO1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: ROBO1 were set to 35348658; 35227688; 34193621; 31448886; 30692597; 29194579; 28592524; 28402530; 28286008 Phenotypes for gene: ROBO1 were set to ROBO1-related NDD Penetrance for gene: ROBO1 were set to unknown Review for gene: ROBO1 was set to AMBER