title: High prevalence of SURF1 c.845_846delCT mutation in Polish Leigh patients.
abstract: Leigh syndrome is a neuropathological disorder with typical morphological changes in brain, appearing regardless of diverse molecular background. One of the most common enzymatic defects in Leigh patients is cytochrome c oxidase deficiency associated with recessive mutations in the SURF1 gene. To assess the SURF1 mutation profile among Polish patients we studied 41 affected children from 34 unrelated families by PCR-SSCP and sequencing. Four novel mutations, c.39delG, c.752-1G>C, c.800_801insT, c.821A>G, and five described pathogenic changes, c.311_312insAT312_321del10, c.688C>T, c.704T>C, c.756_757delCA, c.845_846delCT, were identified in 85.3% of analysed probands. One mutation, c.845_846delCT, was identified in 77.6% of SURF1 alleles. Up to now, it has been reported only in 9% of alleles in other parts of the world. The deletion was used as LS(SURF1-) marker in population studies. Eight heterozygous carriers of the mutation were found in a cohort of 2890 samples. The estimated c.845_846delCT allele frequency is 1:357 (0.28+/-0.2%), and the lowest predicted LS(SURF1-) frequency in Poland 1:126,736.births. Relatively high frequency of LS(SURF1-) in Poland with remarkable c.845_846delCT mutation dominance allows one to start the differential diagnosis of LS in each patient of Polish (and probably Slavonic) origin from the direct search for c.845_846delCT SURF1 mutation.
authors.affiliation: Department of Medical Genetics, Children's Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland. dorota.abr@wp.pl
authors.forename: Dorota
authors.initials: D
authors.lastname: Piekutowska-Abramczuk
authors.forename: Ewa
authors.initials: E
authors.lastname: Popowska
authors.forename: Maciej
authors.initials: M
authors.lastname: Pronicki
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Karczmarewicz
authors.forename: Dorota
authors.initials: D
authors.lastname: Tylek-Lemanska
authors.forename: Jolanta
authors.initials: J
authors.lastname: Sykut-Cegielska
authors.forename: Tamara
authors.initials: T
authors.lastname: Szymanska-Dembinska
authors.forename: Liliana
authors.initials: L
authors.lastname: Bielecka
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Krajewska-Walasek
authors.forename: Ewa
authors.initials: E
authors.lastname: Pronicka
mesh_terms: D030401:Cytochrome-c Oxidase Deficiency / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D005787:Gene Frequency; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007888:Leigh Disease / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000235:genetics*; D009154:Mutation; D011044:Poland / Q000453:epidemiology; D016133:Polymerase Chain Reaction; D015995:Prevalence; D017384:Sequence Deletion
chemical_list: D008565:Membrane Proteins; D024101:Mitochondrial Proteins; C092928:Surf-1 protein