Novel PEX1 mutations in fibroblasts from children with Zellweger spectrum disorders exhibit temperature sensitive characteristics.
Epilepsy Behav
; 145: 109266, 2023 08.
Article
in En
| MEDLINE
| ID: mdl-37385119
ABSTRACT
Zellweger spectrum disorders (ZSD) are rare autosomal recessive disorders caused by defects in peroxisome biogenesis factor (PEX; peroxin) genes leading to impaired transport of peroxisomal proteins with peroxisomal targeting signals (PTS). Four patients, including a pair of homozygotic twins, diagnosed as ZSD by genetic study with different clinical presentations and outcomes as well as various novel mutations are described here. A total of 3 novel mutations, including a nonsense, a frameshift, and a splicing mutation, in PEX1 from ZSD patients were identified and unequivocally confirmed that the p.Ile989Thr mutant PEX1 exhibited temperature-sensitive characteristics and is associated with milder ZSD. The nature of the p.Ile989Thr mutant exhibited different characteristics from that of the other previously identified temperature-sensitive p.Gly843Asp PEX1 mutant. Transcriptome profiles under nonpermissive vs. permissive conditions were explored to facilitate the understanding of p.Ile989Thr mutant PEX1. Further investigation of molecular mechanisms may help to clarify potential genetic causes that could modify the clinical presentation of ZSD.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Zellweger Syndrome
Type of study:
Diagnostic_studies
/
Prognostic_studies
Limits:
Child
/
Humans
Language:
En
Journal:
Epilepsy Behav
Journal subject:
CIENCIAS DO COMPORTAMENTO
/
NEUROLOGIA
Year:
2023
Type:
Article
Affiliation country:
Taiwan