Mapping of the locus for cholestasis-lymphedema syndrome (Aagenaes syndrome) to a 6.6-cM interval on chromosome 15q

Patients with cholestasis-lymphedema syndrome (CLS) suffer severe neonatal cholestasis that usually lessens during early childhood and becomes episodi c; they also develop chronic severe lymphedema. The genetic cause of CLS is unknown. We performed a genome screen, using DNA from eight Norwegian pati ents with CLS and from seven unaffected relatives, all from an extended ped igree. Regions potentially shared identical by descent in patients were fur ther characterized in a larger set of Norwegian patients. The patients mani fest extensive allele and haplotype sharing over the 6.6-cM D15S979-D15S652 region: 30 (83.3%) of 36 chromosomes of affected individuals carry a six-m arker haplotype not found on any of the 32 nontransmitted parental chromoso mes. All Norwegian patients with CLS are likely homozygous for the same dis ease mutation, inherited from a shared ancestor.