Friedreich’s Ataxia: Clinical Presentation of a Compound Heterozygote Child with a Rare Nonsense Mutation and Comparison with Previously Published Cases

Abstract EN

Friedreich’s ataxia is a neurodegenerative disorder associated with a GAA trinucleotide repeat expansion in intron 1 of the frataxin (FXN) gene.

It is the most common autosomal recessive cerebellar ataxia, with a mean age of onset at 16 years.

Nearly 95-98% of patients are homozygous for a 90-1300 GAA repeat expansion with only 2-5% demonstrating compound heterozygosity.

Compound heterozygous individuals have a repeat expansion in one allele and a point mutation/deletion/insertion in the other.

Compound heterozygosity and point mutations are very rare causes of Friedreich’s ataxia and nonsense mutations are a further rarity among point mutations.

We report a rare compound heterozygous Friedrich’s ataxia patient who was found to have one expanded GAA FXN allele and a nonsense point mutation in the other.

We summarize the four previously published cases of nonsense mutations and compare the phenotype to that of our patient.

We compared clinical information from our patient with other nonsense FXN mutations reported in the literature.

This nonsense mutation, to our knowledge, has only been described once previously; interestingly the individual was also of Cuban ancestry.

A comparison with previously published cases of nonsense mutations demonstrates some common clinical characteristics.