ClinVar

In a multiplex consanguineous Algerian family with autosomal recessive optic atrophy (OPA7; 612989), Hanein et al. (2009) identified a c.163C-T transition in the TMEM126A gene, resulting in an arg55-to-ter (R55X) substitution. The mutation occurred in a CpG doublet, segregated with the disease in the family, and was not found in 700 control chromosomes (600 European and 100 Algerian). The same mutation was found in homozygosity in 3 additional autosomal recessive OPA families of Maghrebian origin, 1 from Tunisia and 2 from Morocco. Haplotype analysis was consistent with a founder effect, and suggested that the R55X mutation originated approximately 2,400 years ago.

In 2 affected sibs from a consanguineous family of Algerian origin with optic atrophy and mild sensorineural hearing loss due to auditory neuropathy, Meyer et al. (2010) identified homozygosity for the R55X mutation in the TMEM126A gene. The unaffected parents were heterozygous for the mutation.

In 3 affected sibs from a consanguineous Moroccan family with optic atrophy, Desir et al. (2012) identified homozygosity for the R55X mutation in the TMEM126A gene. The unaffected parents were heterozygous for R55X, as was a brother who experienced transient partial vision loss with exercise (Uhthoff phenomenon) but had normal visual acuity at rest, with no disc pallor on funduscopy. The mutation was not found in 100 ethnically matched controls. The proband also exhibited sensorimotor axonal neuropathy with electrophysiologic data suggestive of focal demyelinating abnormalities.