Role of TOE1 variants at the nuclear localization motif in pontocerebellar hypoplasia 7.
J Hum Genet
; 69(7): 349-355, 2024 Jul.
Article
in En
| MEDLINE
| ID: mdl-38605133
ABSTRACT
Biallelic TOE1 variants can cause pontocerebellar hypoplasia type 7 (PCH7), a condition characterized by pontocerebellar hypoplasia with genital abnormality. TOE1 is a 3'-exonuclese for 3'-end maturation in small nuclear RNA. TOE1 pathogenic variants have been reported at the DEDD catalytic domain and zinc finger motif. Here, we describe a PCH7 patient with novel compound heterozygous TOE1 variants and a detailed clinical course. The patient was a 3-year-old female and showed developmental delay without cerebellar ataxic behavior. Head MRI revealed delayed myelination without pontocerebellar hypoplasia at 9 months of age. Progressive pontocerebellar atrophy was prominent at follow-up MRI. Cerebral abnormalities are characteristic features of PCH7 before pontocerebellar atrophy is observed. One variant, p.Arg331*, was located at the nuclear localization motif (NLM) and partially escaped from nonsense-mediated decay. This variant affected nuclear localization in mutant expressing cells, thus, the TOE1 variant at NLM leads to TOE1 dysfunction associated with nuclear mis-localization.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Nuclear Localization Signals
Limits:
Child, preschool
/
Female
/
Humans
Language:
En
Journal:
J Hum Genet
Journal subject:
GENETICA MEDICA
Year:
2024
Document type:
Article
Affiliation country:
Japan
Country of publication:
United kingdom