Cerebellar and Pontocerebellar Hypoplasia
Gene: EXOSC5
- 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, 11:36 a.m. | Last Modified: 7 Sep 2020, 11:36 a.m.
Panel Version: 0.148
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Cerebellar ataxia, brain abnormalities, and cardiac conduction defects, MIM# 619576; Short stature; Motor developmental delays; Cerebellar hypoplasia; Ataxia
Publications
No phenotype association in OMIM, emerging gene with a single paper
3 patients reported: one patient with cerebellar hypoplasia, another with reduced cerebellar vermis
Summary: 2/3 patients have cerebellar/vermis hypoplasiaCreated: 27 Apr 2020, 3:25 a.m. | Last Modified: 27 Apr 2020, 3:26 a.m.
Panel Version: 0.61
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Developmental delays, short stature, cerebellar hypoplasia and motor weakness
Publications
Phenotypes for gene: EXOSC5 were changed from Short stature; Motor developmental delays; Cerebellar hypoplasia; Ataxia to Cerebellar ataxia, brain abnormalities, and cardiac conduction defects, MIM# 619576; Short stature; Motor developmental delays; Cerebellar hypoplasia; Ataxia
Phenotypes for gene: EXOSC5 were changed from Developmental delays, short stature, cerebellar hypoplasia and motor weakness to Short stature; Motor developmental delays; Cerebellar hypoplasia; Ataxia
Gene: exosc5 has been classified as Green List (High Evidence).
Gene: exosc5 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: EXOSC5 were changed from to Developmental delays, short stature, cerebellar hypoplasia and motor weakness
Publications for gene: EXOSC5 were set to
Mode of inheritance for gene: EXOSC5 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Gene: exosc5 has been classified as Amber List (Moderate Evidence).
gene: EXOSC5 was added gene: EXOSC5 was added to Cerebellar and Pontocerebellar hypoplasia_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: EXOSC5 was set to Unknown