Expanding the neurodevelopmental phenotype associated with HK1 de novo heterozygous missense variants.
Eur J Med Genet
; 66(3): 104696, 2023 Mar.
Article
in En
| MEDLINE
| ID: mdl-36639056
ABSTRACT
Neurodevelopmental disorder with visual defects and brain anomalies (NEDVIBA) is a recently described genetic condition caused by de novo missense HK1 variants. Phenotypic data is currently limited; only seven patients have been published to date. This descriptive case series of a further four patients with de novo missense HK1 variants, alongside integration of phenotypic data with the reported cases, aims to improve our understanding of the associated phenotype. We provide further evidence that de novo HK1 variants located within the regulatory-terminal domain and alpha helix are associated with neurological problems and visual problems. We highlight for the first time an association with a raised cerebrospinal fluid lactate and specific abnormalities to the basal ganglia on brain magnetic resonance imaging, as well as associated respiratory issues and swallowing/feeding difficulties. We propose that this distinctive neurodevelopmental phenotype could arise through disruption of the regulatory glucose-6-phosphate binding site and subsequent gain of function of HK1 within the brain.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Neurodevelopmental Disorders
/
Intellectual Disability
Type of study:
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
Eur J Med Genet
Journal subject:
GENETICA MEDICA
Year:
2023
Document type:
Article