Ataxia and cerebellar anomalies - narrow panel
Gene: OGDHL
The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.Created: 5 Feb 2023, 5:18 p.m. | Last Modified: 5 Feb 2023, 5:18 p.m.
Panel Version: 3.30
Comment on list classification: New gene added by Zornitza Stark. There is sufficient evidence to promote to Green at the next GMS panel update.
The NSRP1 gene is not yet associated with any phenotype in OMIM but has a 'moderate' disease confidence rating in G2P for 'OGDHL-related neurodevelopmental disorder with seizures, hearing loss and gait ataxia'.
At least 10 individuals from 9 unrelated families identified with biallelic variants in this gene (PMIDs: 28017472; 34800363). Main clinical features include mild-to-severe DD/ID (9/10), seizures (5/10), gait ataxia (5/10), profound bilateral sensorineural hearing loss (4/10), spasticity (3/10).Created: 1 Aug 2022, 12:38 p.m. | Last Modified: 1 Aug 2022, 12:38 p.m.
Panel Version: 3.1643
Nine individuals from eight unrelated families carrying bi-allelic variants in OGDHL with a range of neurological and neurodevelopmental phenotypes including epilepsy, hearing
loss, visual impairment, gait ataxia, microcephaly, and hypoplastic corpus callosum.
Homozygous and compound heterozygous variants reported. Variant types reported include missense, PTCs and a synonymous variant that was shown to affect splicing.
Functional studies with a CRISPR-Cas9-mediated tissue knockout with cDNA rescue system showed that the missense variants result in loss-of-function.
Sources: LiteratureCreated: 4 Dec 2021, 2:55 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Neurodevelopmental disorder featuring epilepsy, hearing loss and visual impairment
Publications
Tag Q3_22_rating was removed from gene: OGDHL.
Source Expert Review Green was added to OGDHL. Source NHS GMS was added to OGDHL. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
gene: OGDHL was added gene: OGDHL was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Amber,Literature Q3_22_rating tags were added to gene: OGDHL. Mode of inheritance for gene: OGDHL was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: OGDHL were set to 28017472; 34800363 Phenotypes for gene: OGDHL were set to Yoon-Bellen neurodevelopmental syndrome, OMIM:619701