Cerebellar and Pontocerebellar Hypoplasia

Gene: EXOSC1

Red List (low evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Pontocerebellar hypoplasia, type 1F, MIM# 619304

Red List (low evidence)

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: Literature

Created: 14 Apr 2021, 6:14 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Pontocerebellar hypoplasia

Publications

• PMID: 33463720