Ataxia and cerebellar anomalies - narrow panelGene: EXOSC5
Comment on list classification: Three unrelated families presenting ataxia in association with cerebellar hypoplasia/atrophy. However, all harbour the same p.Thr114Ile variant, and thus it is unclear whether other EXOSC5 variants result in cerebellar ataxia.
Therefore, rating Amber in anticipation of additional publications/clinical evidence.
Created: 7 Sep 2020, 10:36 a.m. | Last Modified: 7 Sep 2020, 10:36 a.m.
Panel Version: 2.10
- PMID: 32504085 (2020) - Five patients from four families with biallelic variants in EXOSC5. Clinical features included short stature (3/5), developmental delays that affect motor skills (3/5), hypotonia (4/5), ataxia (3/4), cerebellar hypoplasia/atrophy (4/5). Cognitive function was generally preserved, but included mild speech delays in one patient.
Cerebellar ataxia was described in two sibs and one singleton - all of whom were compound heterozygous for the p.Thr114Ile variant, inherited in trans with a frameshift variant (p.His30Thrfs*35) or deletion involving exons 5–6 of EXOSC5, respectively.
A LoF zebrafish model resulted in a variety of morphological defects including shortened and curved tails/bodies, reduced eye/head size and oedema. Functional studies of the variants in budding yeast and cultured cells showed some defects in RNA exosome function and interactions, that could not be explained by decrease in the steady-state level of EXOSC5.
- PMID: 29302074 (2019) - Three sibs with a homozygous EXOSC5 variant (p.Thr114Ile), associated with mild motor delays, cerebellar ataxia, nystagmus, dysarthria, and moderate ID. The family is also described in PMID: 30950035. No functional studies of the variant were undertaken.
Created: 7 Sep 2020, 10:27 a.m. | Last Modified: 7 Sep 2020, 10:38 a.m.
Panel Version: 2.10
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Short stature; Motor developmental delays; Cerebellar hypoplasia; Ataxia
Gene: exosc5 has been classified as Amber List (Moderate Evidence).
Publications for gene: EXOSC5 were set to 32504085
gene: EXOSC5 was added gene: EXOSC5 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature Mode of inheritance for gene: EXOSC5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: EXOSC5 were set to 32504085 Phenotypes for gene: EXOSC5 were set to Short stature; Motor developmental delays; Cerebellar hypoplasia; Ataxia