ArticleAnnals of clinical and translational neurology2020
Mutated RAP1GDS1 causes a new syndrome of dysmorphic feature, intellectual disability & speech delay.
Article in Annals of clinical and translational neurology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 20 citations in OpenAlex.
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- Mutated neuron navigator 3 as a candidate gene for a rare neurodevelopmental disorder.Molecular genetics & genomic medicine · 2024Article
- The genetic cause of neurodevelopmental disorders in 30 consanguineous families.Frontiers in medicine · 2024Article
- Vimar/RAP1GDS1 promotes acceleration of brain aging after flies and mice reach middle age.Communications biology · 2023Article
- Congenital disorder of glycosylation with defective fucosylation 2 (FCSK gene defect): The third report in the literature with a mild phenotype.Molecular genetics & genomic medicine · 2023Article
- Systematic gene-disease relationship (GDR) curation unveils 61 gene-disease associations and highlights the impact on genetic testing.Genetics in medicine open · 2023Article
- Novel homozygous pathogenic mitochondrial DNAJC19 variant in a patient with dilated cardiomyopathy and global developmental delay.Molecular genetics & genomic medicine · 2022Article
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- Non-invasive prenatal testing for autosomal recessive disorders: A new promising approach.Frontiers in genetics · 2022Article
- Case Report: Biallelic Variant in the tRNA Methyltransferase Domain of the AlkB Homolog 8 Causes Syndromic Intellectual Disability.Frontiers in genetics · 2022Article
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- Identification of theMolecular syndromology · 2021Article
- SmgGDS: An Emerging Master Regulator of Prenylation and Trafficking by Small GTPases in the Ras and Rho Families.Frontiers in molecular biosciences · 2021Review
- EMC10 homozygous variant identified in a family with global developmental delay, mild intellectual disability, and speech delay.Clinical genetics · 2020Article
- Exploiting the Autozygome to Support Previously Published Mendelian Gene-Disease Associations: An Update.Frontiers in genetics · 2020Article
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11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRAP1GDS1 (RAP1, GTP-GDP dissociation stimulator 1), also known as SmgGDS, is a guanine nucleotide exchange factor (GEF) that regulates small GTPases, including, RHOA, RAC1, and KRAS. RAP1GDS1 was shown to be highly expressed in different tissue types including the brain. However, mutations in the RAP1GDS1 gene associated with human diseases have not previously been reported.
methodsWe report on four affected individuals, presenting intellectual disability, global developmental delay (GDD), and hypotonia. The probands' DNA was subjected to whole-genome sequencing, revealing a homozygous splice acceptor site mutation in the RAP1GDS1 gene (1444-1G > A). Sanger sequencing was performed to confirm the segregation of the variant in two Saudi families. The possible aberrant splicing in the patients' RNA was investigated using RT-PCR and changes in mRNA expression of the patients were confirmed using qRT-PCR.
resultsThe identified splice variant was found to segregate within the two families. RT-PCR showed that the mutation affected RAP1GDS1 gene splicing, resulting in the production of aberrant transcripts in the affected individuals. Quantitative gene expression analysis demonstrated that the RAP1GDS1 mRNA expression in all the probands was significantly decreased compared to that of the control, and Sanger sequencing of the probands' cDNA revealed skipping of exon 13, further strengthening the pathogenicity of this variant.
conclusionWe are the first to report the mutation of the RAP1GDS1 gene as a potential cause of GDD and hypotonia. However, further investigations into the molecular mechanisms involved are required to confirm the role of RAP1GDS1 gene in causing GDD and hypotonia.
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