ORPHA: 95; DO: 0111219;
Cytogenetic location: 9p23-p11 Genomic coordinates (GRCh38): 9:9,000,001-43,000,000
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 9p23-p11 | Friedreich ataxia 2 | 601992 | Autosomal recessive | 2 |
Friedreich ataxia (FRDA) 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 (summary by Delatycki et al., 2000).
For a general phenotypic description of Friedreich ataxia (FRDA), see FRDA1 (229300), which is caused by mutation in the FXN gene (606829) on chromosome 9q13.
Smeyers et al. (1996) reported a nonconsanguineous Spanish family in which 2 adult sibs, a male and a female, had a phenotype consistent with Friedreich ataxia, but linkage excluded the FRDA1 locus on chromosome 9q. The patients had onset of progressive ataxia at ages 10 and 14 years, respectively. Both had areflexia, dysarthria, abnormal sense of joint position, and axonal sensory peripheral neuropathy. Both had pes cavus and one had scoliosis. Neither had evidence of cardiac involvement, and serum vitamin E deficiency was ruled out.
Kostrzewa et al. (1997) reported 2 unrelated families, each with 2 sibs with FRDA. Although the patients studied had typical FRDA, 1 sib pair had the uncommon symptom of retained tendon reflexes. In these families, Kostrzewa et al. (1997) excluded mutations in the FXN gene (606829), and haplotype analysis of the FXN locus on chromosome 9 excluded involvement of this locus. These results provided strong evidence of a second FRDA locus, which the authors termed FRDA2.
In a large consanguineous family from Turkey segregating Friedreich ataxia, Christodoulou et al. (2001) found linkage of the disorder to chromosome 9p23-p11. Multipoint linkage analysis resulted in a maximum lod score of 3.2 at locus D9S43.
Christodoulou, K., Deymeer, F., Serdaroglu, P., Ozdemir, C., Poda, M., Georgiou, D.-M., Ioannou, P., Tsingis, M., Zamba, E., Middleton, L. T. Mapping of the second Friedreich's ataxia (FRDA2) locus to chromosome 9p23-p11: evidence for further locus heterogeneity. Neurogenetics 3: 127-132, 2001. [PubMed: 11523563] [Full Text: https://doi.org/10.1007/s100480100112]
Delatycki, M. B., Williamson, R., Forrest, S. M. Friedreich ataxia: an overview. J. Med. Genet. 37: 1-8, 2000. [PubMed: 10633128] [Full Text: https://doi.org/10.1136/jmg.37.1.1]
Kostrzewa, M., Klockgether, T., Damian, M. S., Muller, U. Locus heterogeneity in Friedreich ataxia. Neurogenetics 1: 43-47, 1997. [PubMed: 10735274] [Full Text: https://doi.org/10.1007/s100480050007]
Smeyers, P., Monros, E., Vilchez, J., Lopez-Arlandis, J., Prieto, F., Palau, F. A family segregating a Friedreich ataxia phenotype that is not linked to the FRDA locus. Hum. Genet. 97: 824-828, 1996. [PubMed: 8641704] [Full Text: https://doi.org/10.1007/BF02346197]