Ataxia and cerebellar anomalies - narrow panelGene: GEMIN5
Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). There is sufficient evidence to promote this gene to Green at the next GMS panel update (see details below).
Kour et al. 2021 (PMID: 33963192) report 30 individuals from 22 unrelated families with biallelic variants in the GEMIN5 gene. All affected individuals displayed predominantly motor DD, although cognitive and speech delays were also seen in most patients (18/19). 23/30 had central hypotonia, and variable appendicular spasticity was observed in 13/30 cases. 8 individuals were nonambulatory, while all ambulatory patients (19) had a gait ataxia. Brain MRI in all cases showed cerebellar atrophy.
Variants perturbed the subcellular distribution, stability, and expression of GEMIN5 protein and its interacting partners, and disrupted snRNP complex assembly formation in patient iPSC-derived neurons, suggesting a LoF mechanism. Knockdown in Drosophila lead to developmental defects, motor dysfunction, and a reduced lifespan
GEMIN5 is associated with a relevant phenotype in OMIM (Neurodevelopmental disorder with cerebellar atrophy and motor dysfunction, MIM# 619333) but is not yet listed in G2P.
Created: 23 Jun 2021, 12:53 p.m. | Last Modified: 23 Jun 2021, 12:53 p.m.
Panel Version: 3.1145
Neurodevelopmental disorder with cerebellar atrophy and motor dysfunction (NEDCAM) is an autosomal recessive disorder characterized by global developmental delay with prominent motor abnormalities, mainly axial hypotonia, gait ataxia, and appendicular spasticity. Affected individuals have cognitive impairment and speech delay; brain imaging shows cerebellar atrophy.
30 individuals from 22 unrelated families reported.
Created: 11 Jun 2021, 9:44 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Neurodevelopmental disorder with cerebellar atrophy and motor dysfunction, MIM# 619333
Variants in this GENE are reported as part of current diagnostic practice
gene: GEMIN5 was added gene: GEMIN5 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Amber,Literature Q2_21_rating tags were added to gene: GEMIN5. Mode of inheritance for gene: GEMIN5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GEMIN5 were set to 33963192 Phenotypes for gene: GEMIN5 were set to Neurodevelopmental disorder with cerebellar atrophy and motor dysfunction, OMIM:619333