Intellectual disability - microarray and sequencing
Gene: NSF
Comment on phenotypes: This gene is now associated with a relevant phenotype in OMIM (MIM #619340), but not in Gene2Phenotype.Created: 17 May 2023, 10:29 a.m. | Last Modified: 17 May 2023, 10:29 a.m.
Panel Version: 5.127
Comment on phenotypes: This gene is now associated with a relevant phenotype in OMIM (MIM #619340), but not in Gene2Phenotype.Created: 17 May 2023, 10:29 a.m. | Last Modified: 17 May 2023, 10:29 a.m.
Panel Version: 5.127
Comment on phenotypes: This gene is now associated with a relevant phenotype in OMIM (MIM #619340), but not in Gene2Phenotype.Created: 17 May 2023, 10:28 a.m. | Last Modified: 17 May 2023, 10:28 a.m.
Panel Version: 5.127
Comment on phenotypes: This gene is now associated with a relevant phenotype in OMIM (MIM #619340), but not in Gene2Phenotype.Created: 17 May 2023, 10:28 a.m. | Last Modified: 17 May 2023, 10:28 a.m.
Panel Version: 5.127
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Developmental and epileptic encephalopathy 96, OMIM:619340
Publications
Not associated with relevant phenotype in OMIM or Gen2Phen (11/05/2021). At least two variants reported in two unrelated cases with epileptic encephalopathy of early infantile onset, one proband died at day 36 after birth of respirative failure, the other proband has profound intellectual disability, severe motor developmental delay, and no spontaneous respiration. Supportive functional studies in Drosophila were also presented (PMID 31675180).Created: 11 May 2021, 6:15 p.m. | Last Modified: 11 May 2021, 6:15 p.m.
Panel Version: 3.1075
Comment on list classification: New gene submitted by expert reviewed. Based on the evidence provided it was decided that there is currently not enough evidence to establish a gene-phenotype association. Therefore, this gene has been given a Red rating.Created: 26 Nov 2019, 2:58 p.m. | Last Modified: 26 Nov 2019, 2:58 p.m.
Panel Version: 2.1117
Suzuki et al. (2019 - PMID: 31675180) report on 2 unrelated individuals with de novo missense NSF variants. Overall the phenotype corresponded to an early infantile epileptic encephalopathy. The first patient developed vomiting and tonic seizures immediately after birth, with burst-suppression pattern upon EEG. Trio exome sequencing, followed by Sanger sequencing of proband and parents, revealed a de novo missense variant (NM_006178.3:c.1375G>A / p.Ala459Thr), absent from public databases and predicted in silico to be deleterious (CADD score of 30). The girl died 36 days after birth due to respiratory failure. Another subject, having necessitated mechanical ventilation due to absence of spontaneous respiration after birth, developed myoclonic seizures. EEG showed a burst-suppression pattern. At the age of 3, she was noted to have persistence of seizures and profound ID. Trio exome sequencing identified a missense NSF variant (c.1688C>T / p.Pro563Leu) also confirmed and shown to be de novo by Sanger sequencing. Again the variant was absent from public datasets and had a CADD score of 34. While expression of wt NSF allele in the developing eye of Drosophila had no effect, expression of mutants severely affected eye development - suggesting a dominant negative effect. NSF encodes a homo-hexameric AAA ATPase, which is recruited by SNAPs (Soluble NSF Attachment Proteins) - and the latter by SNAREs (SNAP REceptors) - thus having a role in vesicular transport and membrane fusion. There is currently no associated phenotype in OMIM/G2P. Overall, this gene could be considered for inclusion probably with amber/red rating pending further evidence (eg. additional work-up or alternative causes/explanations not discussed).
Sources: LiteratureCreated: 11 Nov 2019, 5:36 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Seizures; EEG with burst suppression; Global developmental delay; Intellectual disability
Publications
Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Phenotypes for gene: NSF were changed from Developmental and epileptic encephalopathy 96, OMIM:619340 to Developmental and epileptic encephalopathy 96, OMIM:619340
Phenotypes for gene: NSF were changed from Developmental and epileptic encephalopathy 96, OMIM:619340 to Developmental and epileptic encephalopathy 96, OMIM:619340
Phenotypes for gene: NSF were changed from Developmental and epileptic encephalopathy 96, OMIM:619340 to Developmental and epileptic encephalopathy 96, OMIM:619340
Phenotypes for gene: NSF were changed from Developmental and epileptic encephalopathy 96, OMIM:619340 to Developmental and epileptic encephalopathy 96, OMIM:619340
Phenotypes for gene: NSF were changed from Developmental and epileptic encephalopathy 96, OMIM:619340 to Developmental and epileptic encephalopathy 96, OMIM:619340
Phenotypes for gene: NSF were changed from Seizures; EEG with burst suppression; Global developmental delay; Intellectual disability to Developmental and epileptic encephalopathy 96, OMIM:619340
Publications for gene: NSF were set to 31675180; 36645181
Publications for gene: NSF were set to 31675180
Gene: nsf has been classified as Red List (Low Evidence).
gene: NSF was added gene: NSF was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: NSF was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: NSF were set to 31675180 Phenotypes for gene: NSF were set to Seizures; EEG with burst suppression; Global developmental delay; Intellectual disability Penetrance for gene: NSF were set to unknown Mode of pathogenicity for gene: NSF was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: NSF was set to AMBER