| The Hutterites are a genetically isolated group; their population numbers over 40,000, the majority of whom are descendants of 89 founders. An autosomal recessive neurodevelopmental disorder was identified in four patients from two Hutterite families. The patients have distinctive facial features, congenital malformations of the heart and genitourinary system, borderline microcephaly, and learning disability.;An identity-by-descent mapping approach was used to identify the locus for this disorder. A 50K-SNP microarray identified a single, homozygous region on 16p13.3 shared between the patients. Microsatellite markers genotyped for all available family members refined the locus to a region of 5.1 Mb containing 173 genes. No other recessive disorders with similar clinical features are currently mapped to this region. Genes within the region were prioritized using data mining and expression microarrays. Ninety-seven genes were sequenced. A homozygous variant in THOC6 (p.G46R) was identified and evidence suggests that this variant is disease-causing. |
