GENOMEWIDE SEARCH FOR DEHYDRATED HEREDITARY STOMATOCYTOSIS (HEREDITARY XEROCYTOSIS) - MAPPING OF LOCUS TO CHROMOSOME-16 (16Q23-QTER)

Dehydrated hereditary stomatocytosis, also known as ''hereditary xeroc ytosis,'' is caused by a red blood cell-membrane defect characterized by stomatocytic morphology, increased mean corpuscular hemoglobin conc entration, decreased osmotic fragility, increased permeability to the univalent cations Na+ and K+, and an increased proportion of phosphati dylcholine in the membrane. The clinical presentation is heterogeneous , ranging from mild to moderate hemolytic anemia associated with scler al icterus, splenomegaly, and choletithiasis. Iron overload may develo p later in life. The disease is transmitted as an autosomal dominant t rait. We recruited a large three-generation Irish family affected with DHS and comprising 23 members, of whom 14 were affected and 9 were he althy. Two additional, small families also were included in the study. The DNA samples from the family members were used in a genomewide sea rch to identify, by linkage analysis, the DHS locus. After the exclusi on of a portion of the human genome, we obtained conclusive evidence f or linkage of DHS to microsatellite markers on the long arm of chromos ome 16 (16q23-q24). A maximum two-point LOD score of 6.62 at recombina tion fraction .00 was obtained with marker D16S520. There are no recom bination events defining the telomeric limit of the region, which ther efore is quite large. No candidate genes map to this area.