A novel variant of NEMF in a family with congenital fibrosis of the extraocular muscles: a case report and literature review

Background Congenital fibrosis of the extraocular muscles (CFEOM) is one of the congenital cranial dysinnervation disorders (CCDDs) characterized by hypoplastic oculomotor nerves (CN3), congenital ptosis and non-progressive restrictive ophthalmoplegia. The NEMF gene encodes a protein that resolves stalled ribosomes during translation. Variants in NEMF have been associated with neurodevelopmental and neuromuscular disorders, including intellectual disability, developmental delay, central nervous system impairment and peripheral neuropathy. Case presentation: We describe a family with CFEOM harboring a novel variant of NEMF gene. CFEOM3 was diagnosed in two siblings, a 9 year old girl and a 6 year old boy. Whole-exome sequencing (WES) revealed that the siblings carried a novel heterozygous NEMF variant c.1972A > C, p. (Lys658Gln). This variant was predicted to lead to the loss of hydrogen bonds, potentially affecting the spatial structure and stability of the NEMF protein. Conclusions Our findings support that the NEMF variant may be the cause of CFEOM in our case. This report expands the phenotypic spectrum of NEMF -associated diseases and provides a new candidate gene for CFEOM.