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| Genetic Epilepsy v0.1148 | SYNCRIP |
Konstantinos Varvagiannis gene: SYNCRIP was added gene: SYNCRIP was added to Genetic Epilepsy. Sources: Literature Mode of inheritance for gene: SYNCRIP was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: SYNCRIP were set to 34157790; 30504930; 27479843; 23020937 Phenotypes for gene: SYNCRIP were set to Global developmental delay; Intellectual disability; Autism; Myoclonic atonic seizures; Abnormality of nervous system morphology Review for gene: SYNCRIP was set to AMBER Added comment: Semino et al (2021 - PMID: 34157790) provide clinical details on 3 unrelated individuals with de novo SYNCRIP variants and provide a review of 5 additional subjects previously identified within large cohorts in the literature and databases. Features included DD, ID (7/7 for whom this information was available), ASD or autistic features (4/7). MRI abnormalities were observed in 3 (widening of CSF spaces, periventricular nodular heterotopia, prominent lat. ventricles). Epilepsy (myoclonic-astatic epilepsy / Doose syndrome) was reported for 2(/8) individuals. The 3 patients here reported were identified following trio/singleton exome with Sanger confirmation of the variants and their de novo occurrence. Variants are in almost all cases de novo (7/7 for whom this was known) and in 5/8 cases were pLoF, in 2/8 missense SNVs while a case from DECIPHER had a 77.92 kb whole gene deletion not involving other genes with unknown inheritance. Overall the variants reported to date include [NM_006372.5]: 1 - c.858_859del p.(Gly287Leufs*5) 2 - c.854dupA p.(Asn285Lysfs*8) 3 - c.734T>C p.(Leu245Pro) 4 - chr6:85605276-85683190 deletion (GRCh38) 5 - c.629T>C p.(Phe210Ser) 6 - c.1573_1574delinsTT p.(Gln525Leu) 7 - c.1247_1250del p.(Arg416Lysfs*145) 8 - c.1518_1519insC p.(Ala507Argfs*14) [P1-3: this report, P4: DECIPHER 254774, P5-6: Guo et al 2019 - PMID: 30504930, P7: Lelieveld et al 2016 - PMID: 27479843, P8: Rauch et al 2012 - PMID: 23020937 / all other Refs not here reviewed, clinical details summarized by Semino et al in table 1] SYNCRIP (also known as HNRNPQ) encodes synaptotagmin‐binding cytoplasmic RNA‐interacting protein. As the authors note, this RNA-binding protein is involved in multiple pathways associated with neuronal/muscular developmental disorders. Several references are provided for its involvement in regulation of RNA metabolism, among others sequence recognition, pre-mRNA splicing, translation, transport and degradation. Mutations in other RNA-interacting proteins and hnRNP members (e.g. HNRNPU, HNRNPD) are associated with NDD. The missense variant (p.Leu245Pro) is within RRM2 one of the 3 RNA recognition motif (RRM) domains of the protein. These 3 domains, corresponding to the central part of the protein (aa 150-400), are relatively intolerant to variation (based on in silico predictions and/or variation in gnomAD). Leu245 localizes within an RNA binding pocket and in silico modeling suggests alteration of the tertiary structure and RNA-binding capacity of RRM2. There are no additional studies performed. Overall haploinsufficiency appears to be the underlying disease mechanism based on the truncating variants and the gene deletion. [pLI in gnomAD : 1, %HI : 2.48%] Animal models are not discussed. There is no associated phenotype in OMIM. This gene is included in the DD panel of G2P (monoallelic LoF variants / SYNCRIP-related developmental disorder). SysID also lists SYNCRIP within the current primary ID genes. Sources: Literature |
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| Genetic Epilepsy v0.1006 | HNRNPU | Zornitza Stark Phenotypes for gene: HNRNPU were changed from Epileptic encephalopathy, early infantile, 54, MIM#617391 to Developmental and epileptic encephalopathy 54 MIM# 617391 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genetic Epilepsy v0.570 | HNRNPU | Zornitza Stark Marked gene: HNRNPU as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genetic Epilepsy v0.570 | HNRNPU | Zornitza Stark Gene: hnrnpu has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genetic Epilepsy v0.570 | HNRNPU | Zornitza Stark Phenotypes for gene: HNRNPU were changed from to Epileptic encephalopathy, early infantile, 54, MIM#617391 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genetic Epilepsy v0.569 | HNRNPU | Zornitza Stark Publications for gene: HNRNPU were set to Epileptic encephalopathy, early infantile, 54, MIM#617391 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genetic Epilepsy v0.568 | HNRNPU | Zornitza Stark Publications for gene: HNRNPU were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genetic Epilepsy v0.567 | HNRNPU | Zornitza Stark Mode of inheritance for gene: HNRNPU was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genetic Epilepsy v0.566 | HNRNPU | Zornitza Stark reviewed gene: HNRNPU: Rating: GREEN; Mode of pathogenicity: None; Publications: Epileptic encephalopathy, early infantile, 54, MIM#617391; Phenotypes: 28944577, 28393272; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genetic Epilepsy v0.0 | HNRNPU |
Zornitza Stark gene: HNRNPU was added gene: HNRNPU was added to Genetic Epilepsy_AustralianGenomics_VCGS. Sources: Australian Genomics Health Alliance Epilepsy Flagship,Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: HNRNPU was set to Unknown |
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