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Am J Med Genet A. 2005 Oct 15;138A(3):262-7.

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

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1
Clinic for Special Children, Strasburg, PA 17579, USA. kstrauss@clinicforspecialchildren.org

Abstract

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.

PMID:
16158439
DOI:
10.1002/ajmg.a.30961
[Indexed for MEDLINE]
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