Ataxia and cerebellar anomalies - narrow panel
Gene: EXOSC1Comment on phenotypes: No phenotype in OMIM or in MONDO (21/04/2021)Created: 21 Apr 2021, 1:53 p.m. | Last Modified: 21 Apr 2021, 1:53 p.m.
Panel Version: 2.127
Comment on list classification: Not associated with relevant phenotype in OMIM or Gen2Phen. At least one biallelic variant reported.Created: 21 Apr 2021, 1:53 p.m. | Last Modified: 21 Apr 2021, 1:53 p.m.
Panel Version: 2.126
Comment on phenotypes: No phenotype listed in OMIM or in MONDO (21/04/2021)Created: 21 Apr 2021, 1:46 p.m. | Last Modified: 21 Apr 2021, 1:46 p.m.
Panel Version: 2.125
Comment on list classification: Not associated with relevant phenotype in OMIM or Gen2Phen. At least one biallelic variant reported (PMID 33463720).Created: 21 Apr 2021, 1:45 p.m. | Last Modified: 21 Apr 2021, 1:45 p.m.
Panel Version: 2.124
An 8‐months‐old male with developmental delay, microcephaly, subtle dysmorphism, hypotonia, pontocerebellar hypoplasia and delayed myelination. Similarly affected elder sibling succumbed at the age of 4‐years 6‐months. Exome sequencing revealed a homozygous missense variant (c.104C >T, p.Ser35Leu) in EXOSC1. In silico mutagenesis revealed loss of a polar contact with neighbouring Leu37 residue. Quantitative real‐time PCR indicated no appreciable differences in EXOSC1 transcript levels. Immunoblotting and blue native PAGE revealed reduction in the EXOSC1 protein levels and EXO9 complex in the proband, respectively. Of note, bi‐allelic variants in other exosome subunits EXOSC3, EXOSC8 and EXOSC9 have been reported to cause pontocerebellar hypoplasia type 1B, type 1C and type 1D, respectively.
Sources: LiteratureCreated: 19 Apr 2021, 9:52 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Pontocerebellar hypoplasia
Publications
Phenotypes for gene: EXOSC1 were changed from Pontocerebellar hypoplasia to Pontocerebellar hypoplasia
Gene: exosc1 has been classified as Red List (Low Evidence).
Phenotypes for gene: EXOSC1 were changed from Pontocerebellar hypoplasia to Pontocerebellar hypoplasia
Gene: exosc1 has been classified as Red List (Low Evidence).
gene: EXOSC1 was added gene: EXOSC1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature Mode of inheritance for gene: EXOSC1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: EXOSC1 were set to 33463720 Phenotypes for gene: EXOSC1 were set to Pontocerebellar hypoplasia Review for gene: EXOSC1 was set to RED