Ataxia and cerebellar anomalies - narrow panel

Gene: EEFSEC

Green List (high evidence)

Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS update.

Created: 2 Feb 2025, 12:02 a.m. | Last Modified: 2 Feb 2025, 12:02 a.m.

Panel Version: 7.15

Comment on publications: PMID:39753114 paper was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.

Created: 1 Feb 2025, 11:16 p.m. | Last Modified: 1 Feb 2025, 11:16 p.m.

Panel Version: 7.14

PMID:39753114 reported nine different individuals from eight unrelated families with a selenopathy with early-onset neurodegeneration. Thy were all identified with six different biallelic variants in EEFSEC gene, of which seven families had variants in homozygous state, while one family had variants in compound heterozygous state. They presented with global developmental delay, moderate or severe cognitive impairment, progressive spasticity, ataxia, and seizures. In addition, cerebral MRI primarily demonstrated a cerebellar pathology, including hypoplasia and progressive atrophy. Ataxia was reported in four unrelated cases, cerebellar hypoplasia in one and cerebellar atrophy in four cases from three families.

In line with the clinical phenotype, an eEFSec-RNAi Drosophila model displays progressive impairment of motor function, which is reflected in the synaptic defects in this model organisms.

This gene has not yet been associated with any relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature

Created: 1 Feb 2025, 9:58 p.m. | Last Modified: 2 Feb 2025, 12:04 a.m.

Panel Version: 7.15

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
neurodevelopmental disorder, MONDO:0700092; hereditary cerebellar ataxia, MONDO:0100310

Publications

• 39753114