Gene responsible for mitochondrial myopathy and sideroblastic anemia (MSA) maps to chromosome 12q24.33

Am J Med Genet A. 2004 May 15;127A(1):44-9. doi: 10.1002/ajmg.a.20652.


Mitochondrial myopathy and sideroblastic anemia (MSA) is a rare autosomal recessive disorder of oxidative phosphorylation and iron metabolism. Individuals with MSA present with weakness and anemia in late childhood and may become dependent on blood transfusions. Recently, we reported affected sibling pairs from a Jewish-Iranian kindred living in the US [Casas and Fischel-Ghodsian, 2003]. A genome scan and fine mapping of DNA from this family revealed homozygous alleles in the affected individuals, and a multipoint logarithm of the odds (lod) score of 3.3, within 2.3 mb of chromosome 12q24.33. Previously, Inbal et al. [1995: Am J Med Genet 55:372-378] described siblings with a similar clinical phenotype who lived in Israel but originated from the same Iranian town as the US family. Focused analysis of DNA from the Israeli family confirmed the presence of identical, homozygous alleles in the affected of the US and Israeli families within 1.2 mb of chromosome 12q24.33. Combined multipoint linkage analysis revealed a maximum lod score of 5.41 at the 132 cM position of chromosome 12. Therefore, in these two families of Jewish-Iranian descent, a disease gene for MSA maps to a 1.2 mb region of chromosome 12q24.33. This region contains 6 well described genes (SFRS8, MMP17, ULK1, PUS1, EP400, and GALNT9) and at least 15 additional putative transcripts. The known genes are expressed in multiple tissues and lack a function specific to mitochondria, making none an obvious candidate. The eventual identification of the disease gene in MSA is expected to provide insight into the tissue specificity and phenotypic variability of mitochondrial disease.

Publication types

  • Case Reports
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Anemia, Sideroblastic / diagnosis
  • Anemia, Sideroblastic / genetics*
  • Chromosome Mapping
  • Chromosomes, Human, Pair 12 / genetics*
  • DNA Fingerprinting
  • Female
  • Humans
  • Male
  • Microsatellite Repeats
  • Middle Aged
  • Mitochondrial Myopathies / diagnosis
  • Mitochondrial Myopathies / genetics*
  • Pedigree
  • Polymorphism, Single Nucleotide