Novel Germline ELP1 Splice-Acceptor Variant in NF1-Negative Optic Pathway Glioma: Expanding the Clinical Spectrum Associated With ELP1 Variation.

Germline splice-acceptor variant in ELP1, a tumour predisposition with incomplete penetrance.

The authors report a 7-year-old boy with an NF1-negative optic pathway glioma in whom exome sequencing identified a novel germline ELP1 splice-acceptor variant (NM_003640.5:c.2205-2A>G). The variant was classified as likely pathogenic under ACMG/AMP criteria (PVS1, PM2). It was inherited from an asymptomatic father, consistent with incomplete penetrance. This observation expands the still-limited evidence linking germline ELP1 variation to gliomas.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The practical takeaway is to consider ELP1 in an optic pathway glioma without an NF1 variant, a setting where exome sequencing retains its full value. This is nonetheless a single case, with no functional validation of the splicing effect, and inheritance from an asymptomatic father makes genetic counselling difficult: no risk figure can be given to carrier relatives at this stage. To be taken as one more piece of the ELP1 file, not as a surveillance indication.

Analysis by Dr Thibaut Benquey