LINKAGE ANALYSIS OF A LARGE PEDIGREE WITH HEREDITARY SIDEROBLASTIC ANEMIA

A large pedigree showing a history of pyridoxine responsive X linked s ideroblastic anaemia was screened with several polymorphic DNA markers from the X chromosome. Linkage analysis between each marker and disea se status was performed, giving a maximum two point lod score of 3.64 at zero recombination with the microsatellite marker PGK1P1 at Xq11.2- 12. Close linkage to PGK at Xq13.3, one of the candidate regions for X linked sideroblastic anaemia, was excluded. Linkage to DNA markers di stal to PGK and at Xp21 was also excluded. Multipoint linkage analysis was performed with markers located between Xq11.2-21. The maximum map specific lod score obtained was 3.56 at PGK1P1 (Xq11.2-12). Linkage r emained significant over the interval 20 cM proximal to PGK1P1 and 5cM distal to PGK1P1, with definite exclusion around the PGK locus. The m ost likely location of the gene involved in sideroblastic anaemia in t his pedigree is therefore within the pericentromeric region of the X c hromosome. This region includes the erythroid 5-aminolaevulinate synth etase gene of the haem synthesis pathway, which is a candidate gene fo r X linked sideroblastic anaemia located at Xp11.21.