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Intellectual disability v9.55 RREB1 Achchuthan Shanmugasundram changed review comment from: PMID:38332451 (2024) reported the first patient with RREB1-associated Noonan-like RASopathy. A pathogenic de novo variant in RREB1 gene was identified by whole-genome sequencing and was confirmed by Sanger sequencing in the proband (c.2677del/ p.Ala893Argfs*20). The patient presented with severe intellectual disability, delayed motor skills, short stature, short neck, and distinctive facial dysmorphisms.

PMID:40418122 reported a cohort of six individuals with a RASopathy phenotype, which include mild dysmorphisms, congenital heart disease, genitourinary malformations, dental anomalies, and developmental delay. Global developmental delay was reported in two of these six patients. They were identified with six different truncating RREB1 variants via exome sequencing (five patients with de novo and one patient with paternally inherited variants).

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.; to: PMID:38332451 (2024) reported the first patient with RREB1-associated Noonan-like RASopathy. A pathogenic de novo variant in RREB1 gene was identified by whole-genome sequencing and was confirmed by Sanger sequencing in the proband (c.2677del/ p.Ala893Argfs*20). The patient presented with severe intellectual disability, delayed motor skills, short stature, short neck, and distinctive facial dysmorphisms.

PMID:40418122 (2025) reported a cohort of six individuals with a RASopathy phenotype, which include mild dysmorphisms, congenital heart disease, genitourinary malformations, dental anomalies, and developmental delay. Global developmental delay was reported in two of these six patients. They were identified with six different truncating RREB1 variants via exome sequencing (five patients with de novo and one patient with paternally inherited variants).

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Intellectual disability v9.55 RREB1 Achchuthan Shanmugasundram changed review comment from: PMID:38332451 (2024) reported the first patient with RREB1-associated Noonan-like RASopathy. A pathogenic de novo variant in RREB1 gene was identified by whole-genome sequencing and was confirmed by Sanger sequencing in the proband (c.2677del/ p.Ala893Argfs*20). The patient presented with severe intellectual disability and general muscular hypotonia among other features.

PMID:40418122 reported a cohort of six individuals with a RASopathy phenotype, which include mild dysmorphisms, congenital heart disease, genitourinary malformations, dental anomalies, and developmental delay. Global developmental delay was reported in two of these six patients. They were identified with six different truncating RREB1 variants via exome sequencing (five patients with de novo and one patient with paternally inherited variants).

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.; to: PMID:38332451 (2024) reported the first patient with RREB1-associated Noonan-like RASopathy. A pathogenic de novo variant in RREB1 gene was identified by whole-genome sequencing and was confirmed by Sanger sequencing in the proband (c.2677del/ p.Ala893Argfs*20). The patient presented with severe intellectual disability, delayed motor skills, short stature, short neck, and distinctive facial dysmorphisms.

PMID:40418122 reported a cohort of six individuals with a RASopathy phenotype, which include mild dysmorphisms, congenital heart disease, genitourinary malformations, dental anomalies, and developmental delay. Global developmental delay was reported in two of these six patients. They were identified with six different truncating RREB1 variants via exome sequencing (five patients with de novo and one patient with paternally inherited variants).

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Intellectual disability v9.55 RREB1 Achchuthan Shanmugasundram Tag Q3_25_promote_green tag was added to gene: RREB1.
Tag Q3_25_NHS_review tag was added to gene: RREB1.
Intellectual disability v9.55 RREB1 Achchuthan Shanmugasundram Classified gene: RREB1 as Amber List (moderate evidence)
Intellectual disability v9.55 RREB1 Achchuthan Shanmugasundram Added comment: Comment on list classification: Of the seven unrelated patients reported with monoallelic single nucleotide variants in RREB1 gene, three were reported with either intellectual disability or global developmental delay. Hence, this gene can be promoted to green rating in the next GMS update.
Intellectual disability v9.55 RREB1 Achchuthan Shanmugasundram Gene: rreb1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v9.54 RREB1 Achchuthan Shanmugasundram Publications for gene: RREB1 were set to 38332451; 40418122
Intellectual disability v9.53 RREB1 Achchuthan Shanmugasundram Phenotypes for gene: RREB1 were changed from Rasopathy; Noonan-like; developmental disorder to RASopathy, MONDO:0021060
Intellectual disability v9.53 RREB1 Achchuthan Shanmugasundram Publications for gene: RREB1 were set to PMID: 40418122
Intellectual disability v9.52 RREB1 Achchuthan Shanmugasundram reviewed gene: RREB1: Rating: GREEN; Mode of pathogenicity: None; Publications: 38332451, 40418122; Phenotypes: RASopathy, MONDO:0021060; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v9.51 RREB1 Karen Stals gene: RREB1 was added
gene: RREB1 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: RREB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RREB1 were set to PMID: 40418122
Phenotypes for gene: RREB1 were set to Rasopathy; Noonan-like; developmental disorder
Penetrance for gene: RREB1 were set to Complete
Review for gene: RREB1 was set to GREEN
Added comment: 6 additional individuals with truncating variants in RREB1 gene and a Rasopathy phenotype, features including congenital heart disease, developmental delay, short stature, and dysmorphic facial features (PMID: 40418122). RREB1 encodes a transcriptional repressor of Ras-MAPK signalling. Supporting functional evidence and animal models.
Sources: Literature