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| Intellectual disability - microarray and sequencing v3.1083 | TSEN15 | Arina Puzriakova Phenotypes for gene: TSEN15 were changed from delayed developmental milestones; Pontocerebellar hypoplasia, type 2F, 617026; Intellectual disability to Pontocerebellar hypoplasia, type 2F, OMIM:617026 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.978 | TSEN15 |
Catherine Snow Added phenotypes Pontocerebellar hypoplasia, type 2F, 617026 for gene: TSEN15 Publications for gene TSEN15 were changed from 27392077; 25558065 to 27392077; 30914295; 25558065 |
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| Intellectual disability - microarray and sequencing v2.834 | TSEN15 | Rebecca Foulger Added comment: Comment on publications: One of the individuals in family II reported by Breuss et al. (PMID:27392077) was previously included in a study by Alazami et al (PMID:25558065). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.834 | TSEN15 | Rebecca Foulger Publications for gene: TSEN15 were set to 27392077; 25558065 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.829 | TSEN15 | Rebecca Foulger Tag watchlist tag was added to gene: TSEN15. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.829 | TSEN15 | Rebecca Foulger Phenotypes for gene: TSEN15 were changed from Pontocerebellar hypoplasia, type 2F, 617026 to Pontocerebellar hypoplasia, type 2F, 617026; Intellectual disability; delayed developmental milestones | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.828 | TSEN15 | Rebecca Foulger Classified gene: TSEN15 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.828 | TSEN15 | Rebecca Foulger Added comment: Comment on list classification: TSEN15 was added to the ID panel and rated Green by Konstantinos Varvagiannis based on PMID:27392077 (Breuss et al., 2016) who report three homozygous TSEN15 variants in four individuals from three families. Affected individuals showed progressive microcephaly, delayed developmental milestones, variable intellectual disability (and in 2 of 4 cases, epilepsy). Although there are three unrelated cases, I have rated TSEN15 as Amber (borderline) for now because The His116Tyr variant found in the two individuals from Family III had no effect on the level of expression of TSEN15 (but may instead result in destabilization of the complex) and the ID is only mild-moderate in Family III. Added a 'watchlist' tag awaiting further cases. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.828 | TSEN15 | Rebecca Foulger Gene: tsen15 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.827 | TSEN15 | Rebecca Foulger Phenotypes for gene: TSEN15 were changed from Pontocerebellar hypoplasia, type 2F (MIM 617026) to Pontocerebellar hypoplasia, type 2F, 617026 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability - microarray and sequencing v2.588 | TSEN15 |
Konstantinos Varvagiannis gene: TSEN15 was added gene: TSEN15 was added to Intellectual disability. Sources: Literature,Radboud University Medical Center, Nijmegen Mode of inheritance for gene: TSEN15 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TSEN15 were set to 27392077; 25558065 Phenotypes for gene: TSEN15 were set to Pontocerebellar hypoplasia, type 2F (MIM 617026) Penetrance for gene: TSEN15 were set to Complete Review for gene: TSEN15 was set to GREEN gene: TSEN15 was marked as current diagnostic Added comment: Biallelic pathogenic variants in TSEN15 cause Pontocerebellar hypoplasia, type 2F (MIM 617026). Four individuals with molecular confirmation of the diagnosis, from 3 unrelated consanguineous families have been reported by Breuss et al. (PMID: 27392077). One of these individuals was previously included in a study of neurogenetic disorders in consanguineous families (Alazami et al. - PMID: 25558065). A similarly affected sib (possibly not tested) was reported for one patient. DD with variable degrees of ID (mild to severe), progressive microcephaly were common to all. Seizures were noted in 2 individuals. MRI images (for the feature of pontocerebellar hypoplasia - PCH) were only available for 2 families. Affected subjects were homozygous for missense variants private to each family, namely: - NM_052965.3:c.226T>G (p.Trp76Gly) - NM_052965.3:c.346C>T (p.His116Tyr) - NM_052965.3:c.455A>G (p.Tyr152Cys) Trp76Gly and Tyr152Cys resulted in reduced protein abundance while His116Tyr did not have an effect on TSEN15 expression levels. TSEN15 is part of the tRNA splicing endonuclease complex, the 3 other components of which (TSEN2, TSEN34, TSEN54) have already been associated with PCH. The complex interacts with an RNA kinase encoded by CLP1. All 3 variants resulted in altered stoichiometry (/relative abundance) of the 3 other subunits of the complex as well as the relative levels of CLP1. Almost complete loss of in vitro tRNA cleavage activity was the case for purified complexes from all 3 mutants. ------ TSEN15 is included in the DD panel of G2P associated with Pontocerebellar Hypoplasia and Progressive Microcephaly (Disease confidence: probable). ID is among the assigned phenotypes. This gene is included in gene panels for ID offered by diagnostic laboratories (incl. Radboudumc). ------ As a result, TSEN15 could be considered for inclusion in this panel as green (or amber). Sources: Literature, Radboud University Medical Center, Nijmegen |
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