The gene for leukoencephalopathy with vanishing white matter is located onchromosome 3q27

Leukoencephalopathy with vanishing white matter (VWM) is an autosomal reces sive disorder with normal early development and, usually, childhood-onset n eurological deterioration. At present, diagnosis of VWM is based on clinica l examination and the results of repeat magnetic resonance imaging and magn etic resonance spectroscopy, which show that,with time, increasing amounts of the cerebral white matter vanish and are replaced by cerebrospinal fluid . We have performed a genome linkage screening of a panel of 19 families of different ethnic origins. Significant linkage to chromosome 3q27 was obser ved in a 7-cM interval between markers D3S3730 and D3S3592, with a maximum multipoint LOD score of 5.1 calculated from the entire data set. The result s of genealogical studies have suggested that seven parents in four Dutch f amilies with VWM may have inherited an allele for the disease from a common ancestor who lived at least eight generations ago. Analysis of these famil ies provided further evidence for the localization of the gene for VWM to 3 q27. The patients shared a haplotype spanning 5 cM between markers D3S1618 and D3S3592. In one family of a different ethnic background, the patient ha d, in the same region, homozygosity for 13 consecutive markers spanning at least 12 cM, suggesting consanguinity between the parents. A healthy siblin g of this patient had the same homozygous haplotype, which suggests that th e healthy sibling is presymptomatic for the disease.