Haploinsufficiency of POU4F1 causes an ataxia syndrome with hypotonia and intention tremor.
Hum Mutat
; 42(6): 685-693, 2021 06.
Article
em En
| MEDLINE
| ID: mdl-33783914
ABSTRACT
De novo, heterozygous, loss-of-function variants were identified in Pou domain, class 4, transcription factor 1 (POU4F1) via whole-exome sequencing in four independent probands presenting with ataxia, intention tremor, and hypotonia. POU4F1 is expressed in the developing nervous system, and mice homozygous for null alleles of Pou4f1 exhibit uncoordinated movements with newborns being unable to successfully right themselves to feed. Head magnetic resonance imaging of the four probands was reviewed and multiple abnormalities were noted, including significant cerebellar vermian atrophy and hypertrophic olivary degeneration in one proband. Transcriptional activation of the POU4F1 p.Gln306Arg protein was noted to be decreased when compared with wild type. These findings suggest that heterozygous, loss-of-function variants in POU4F1 are causative of a novel ataxia syndrome.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ataxia
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Tremor
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Fator de Transcrição Brn-3A
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Hipotonia Muscular
Tipo de estudo:
Diagnostic_studies
/
Etiology_studies
/
Observational_studies
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Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
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Child
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Child, preschool
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Female
/
Humans
/
Male
País/Região como assunto:
America do norte
Idioma:
En
Revista:
Hum Mutat
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos