Genome-wide SNP arrays as a diagnostic tool: clinical description, genetic mapping, and molecular characterization of Salla disease in an Old Order Mennonite population

Am J Med Genet A. 2005 Oct 15;138A(3):262-7. doi: 10.1002/ajmg.a.30961.


An Old Order Mennonite child was evaluated for gross motor delay, truncal ataxia, and slow linear growth. The diagnostic evaluation, which included sub-specialty consultations, neuroimaging, and metabolic testing, was long, costly, and did not yield a diagnosis. Recognition of a similarly affected second cousin prompted a genome-wide homozygosity mapping study using high-density single nucleotide polymorphism (SNP) arrays. SNP genotypes from two affected individuals and their parents were used to localize the disease locus to a 14.9 Mb region on chromosome 6. This region contained 55 genes, including SLC17A5, the gene encoding the lysosomal N-acetylneuraminic acid transport protein. Direct sequencing of SLC17A5 in the proband revealed homozygosity for the 115C --> T (R39C) sequence variant, the common cause of Salla disease in Finland. Three additional affected Mennonite individuals, ages 8 months to 50 years, were subsequently identified by directed molecular genetic testing. This small-scale mapping study was rapid, inexpensive, and analytically simple. In families with shared genetic heritage, genome-wide SNP arrays with relatively high marker density allow disease gene mapping studies to be incorporated into routine diagnostic evaluations.

MeSH terms

  • Agenesis of Corpus Callosum
  • Child
  • Child, Preschool
  • Chromosome Mapping*
  • Corpus Callosum / diagnostic imaging
  • Cross-Cultural Comparison
  • Developmental Disabilities / diagnosis
  • Developmental Disabilities / genetics
  • Female
  • Genomics
  • Humans
  • Infant
  • Magnetic Resonance Spectroscopy
  • Male
  • Middle Aged
  • Organic Anion Transporters / genetics
  • Pedigree
  • Polymorphism, Single Nucleotide*
  • Protestantism
  • Radiography
  • Sialic Acid Storage Disease / diagnosis*
  • Sialic Acid Storage Disease / genetics*
  • Symporters / genetics


  • Organic Anion Transporters
  • Symporters
  • sialic acid transport proteins