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General Information
Name
Friedreich ataxia 1
FlyBase ID
FBhh0000149
Overview

This report describes Friedreich ataxia 1 (FRDA), which exhibits autosomal recessive inheritance. The human gene implicated in this disease is FXN, which encodes frataxin, a nuclear-encoded mitochondrial iron chaperone involved in iron-sulfur biogenesis and heme biosynthesis. The most common FRDA-related molecular abnormality is an expansion of a non-coding GAA triplet repeat in the first intron of the FXN gene. There is one high-scoring fly ortholog, fh for which an amorphic allele, RNAi targeting constructs, and alleles caused by insertional mutagenesis have been generated.

UAS constructs of the wild-type human Hsap\FXN gene have been introduced into flies. Heterologous rescue (functional complementation) of Dmel\fh phenotypes has been demonstrated.

Animals homozygous for an amorphic allele of Dmel\fh die during late larval or pupal stages; somatic clones exhibit neuroanatomy and neurophysiology defects. A moderate loss of function, effect by RNAi, results in a shortened life span, reduced climbing abilities, and enhanced sensitivity to oxidative stress; loss of function targeted specifically to the developing heart results in cardiac defects. An expanded GAA triplet-repeat from the first intron of the human Hsap\FXN gene, with a GAA repeat length of about 200 units and obtained from the genomic DNA of a patient with FRDA, has been inserted into the intron of the Dmel\fh gene. These flies exhibit loss-of-function phenotypes. Genetic interactions of Dmel\fh have been described; see the fh gene report.

[updated Mar. 2021 by FlyBase; FBrf0222196]

Disease Summary Information
Disease Summary: Friedreich ataxia 1
OMIM report

[FRIEDREICH ATAXIA; FRDA](https://omim.org/entry/229300)

Human gene(s) implicated

[FRATAXIN; FXN](https://omim.org/entry/606829)

Symptoms and phenotype

Friedreich ataxia is an autosomal recessive neurodegenerative disorder characterized by progressive gait and limb ataxia with associated limb muscle weakness, absent lower limb reflexes, extensor plantar responses, dysarthria, and decreased vibratory sense and proprioception. Onset is usually in the first or second decade, before the end of puberty. It is one of the most common forms of autosomal recessive ataxia, occurring in about 1 in 50,000 individuals. Other variable features include visual defects, scoliosis, pes cavus, and cardiomyopathy (review by Delatycki et al., 2000, pubmed:10633128). [From OMIM:229300, 2016.01.22]

Genetics

Friedreich ataxia (FRDA1) is caused by mutation in FXN, the gene encoding frataxin. The most common molecular abnormality is a noncoding GAA trinucleotide repeat expansion in intron 1 of the FXN gene: normal individuals have 5 to 30 GAA repeat expansions, whereas affected individuals have from 70 to more than 1,000 GAA triplets (Al-Mahdawi et al., 2006, pubmed:16919418). 2% of cases of Friedreich ataxia are due to point mutations in the FXN gene (Delatycki et al., 1999, pubmed:10543403). [From OMIM:229300, 2016.01.22]

Cellular phenotype and pathology
Molecular information

Frataxin is a nuclear-encoded mitochondrial iron chaperone involved in iron-sulfur biogenesis and heme biosynthesis. Some studies have also suggested that frataxin functions as an iron storage molecule, an antioxidant, and a tumor suppressor (summary by Schmucker et al., 2008,pubmed:18725397). [From OMIM:606829, 2016.01.22]

External links
Disease synonyms
FA
FARR
FRDA
FRDA1
Friedreich's ataxia
Friedreich's tabes
Friedreich ataxia
Friedreich ataxia 1; FRDA
Friedreich ataxia with retained reflexes
Ortholog Information
Human gene(s) in FlyBase
Human gene (HGNC)
Symbol / Name
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)

One to one: 1 human to 1 Drosophila.

Other mammalian ortholog(s) used
    D. melanogaster Gene Information (1)
    Gene Snapshot
    frataxin (fh) encodes an essential nuclear encoded protein located in the mitochondrial inner membrane. It is involved in the synthesis of iron-sulfur clusters which are required for ATP production by the respiratory chain as well as other biological processes such as steroidogenesis. The levels of the product of fh are also crucial for protection of the product of mAcon1 against oxidative stress and iron homeostasis. [Date last reviewed: 2019-03-07]
    Gene Groups / Pathways
    Comments on ortholog(s)

    Ortholog of human FXN (1 Drosophila to 1 human).

    Dmel\fh shares 42% identity and 57% similarity with human FXN.

    Orthologs and Alignments from DRSC
    DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
    Other Genes Used: Viral, Bacterial, Synthetic (0)
      Summary of Physical Interactions (0 groups)
      Alleles Reported to Model Human Disease (Disease Ontology) (11 alleles)
      Models Based on Experimental Evidence ( 6 )
      Modifiers Based on Experimental Evidence ( 6 )
      Allele
      Disease
      Interaction
      References
      is ameliorated by fh+t3.3
      is ameliorated by fhUAS.cAa
      is ameliorated by fhUAS.Tag:V5
      is ameliorated by laceKK102282
      is ameliorated by Pdk1KK108363
      is ameliorated by Mef2GD5039
      Models Based on Experimental Evidence ( 0 )
      Allele
      Disease
      Evidence
      References
      Modifiers Based on Experimental Evidence ( 2 )
      Allele
      Disease
      Interaction
      References
      Alleles Representing Disease-Implicated Variants
      Genetic Tools, Stocks and Reagents
      Sources of Stocks
      Contact lab of origin for a reagent not available from a public stock center.
      Bloomington Stock Center Disease Page
      Selected mammalian transgenes
      Allele
      Transgene
      Publicly Available Stocks
      Selected Drosophila transgenes
      Allele
      Transgene
      Publicly Available Stocks
      RNAi constructs available
      Allele
      Transgene
      Publicly Available Stocks
      Selected Drosophila classical alleles
      Allele
      Allele class
      Mutagen
      Publicly Available Stocks
      gene targeting by homologous recombination
      gene targeting by homologous recombination
      amorphic allele - genetic evidence
      ethyl methanesulfonate
      References (44)