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June 4, 2026Annals of Clinical and Translational Neurology0 citationsOpen Access

Compound Heterozygote Friedreich Ataxia Patients With Covert Proximal FXN Gene Deletions

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MLMichael P. LazaropoulosMDMorgan C. DevoreCLChristina Lam

Key Points

  • This study aims to highlight the presence and impact of covert proximal frataxin gene deletions in Friedreich ataxia patients.
  • Data collected from patients enrolled in the FACOMS natural history study at the Children's Hospital of Philadelphia.
  • Clinical records of patients with proximal deletions diagnosed with one GAA expanded allele were analyzed.
  • Comparative analysis with patients having homozygous expansions and other pathogenic variants was conducted.
  • Patients with proximal deletions exhibited more severe disease symptoms compared to homozygous expansion patients.
  • Increased frequency of associated conditions such as cardiomyopathy (increased risk), diabetes, and optic neuropathy was observed.
  • Phenotypic similarities were noted between patients with covert deletions and those with distal deletions or null pathogenic variants.

Abstract

We present Friedreich ataxia patients with frataxin gene deletions. Data and records were collected at the Children's Hospital of Philadelphia from patients enrolled in the FACOMS natural history study. Patients with proximal deletions initially diagnosed with only one GAA expanded allele had more severe disease than their homozygous expansion counterparts, including increased frequency of cardiomyopathy, diabetes, and optic neuropathy. Their phenotypes were like those of individuals with distal deletions and null pathogenic variants in the frataxin gene. Covert proximal frataxin gene deletions should be suspected when genetic testing fails to demonstrate two distinct expanded alleles in patients with severe phenotypes.

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Cite This Study

Lazaropoulos et al. (2026) studied this question.

synapsesocial.com/papers/6a211670d499ed480b16f65bhttps://doi.org/10.1002/acn3.70408
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