A Novel Truncating Pathogenic Variant in RRM2B in a Kurdish Family With Autosomal-Dominant Chronic Progressive External Ophthalmoplegia Plus (PEOA5).

OBJECTIVES

To report a family with autosomal-dominant chronic progressive external ophthalmoplegia due to a novel truncating pathogenic variant in RRM2B and to show the challenges facing clinicians in diagnosing rare neuromuscular diseases.

METHODS

Four family members were examined. Muscle biopsy, mitochondrial DNA analysis, next generation sequencing, and targeted mitochondrial gene panel followed by Sanger sequencing and complementary deoxyribonucleic acid analysis were performed.

RESULTS

A novel heterozygous RRM2B truncating variant c.968_972del p.(Phe323*) was identified. complementary deoxyribonucleic acid analysis showed expression of both RRM2B alleles.

CONCLUSIONS

The proband was initially misdiagnosed as myasthenia gravis. Based on the phenotype and family history, chronic progressive external ophthalmoplegia was suspected and confirmed by finding of a novel RRM2B variant. The detection of another truncating pathogenic variant in exon 9 of RRM2B further supports this exon as mutation hot spot and underlines the role of the C-terminal highly conserved amino acids for the interaction of the p53R2 dimer with the R1 dimer.