Genomewide search for dehydrated hereditary stomatocytosis (hereditary xerocytosis): mapping of locus to chromosome 16 (16q23-qter)

Abstract

Dehydrated hereditary stomatocytosis, also known as "hereditary xerocytosis," is caused by a red blood cell-membrane defect characterized by stomatocytic morphology, increased mean corpuscular hemoglobin concentration, decreased osmotic fragility, increased permeability to the univalent cations Na+ and K+, and an increased proportion of phosphatidylcholine in the membrane. The clinical presentation is heterogeneous, ranging from mild to moderate hemolytic anemia associated with scleral icterus, splenomegaly, and choletithiasis. Iron overload may develop later in life. The disease is transmitted as an autosomal dominant trait. We recruited a large three-generation Irish family affected with DHS and comprising 23 members, of whom 14 were affected and 9 were healthy. Two additional, small families also were included in the study. The DNA samples from the family members were used in a genomewide search to identify, by linkage analysis, the DHS locus. After the exclusion of a portion of the human genome, we obtained conclusive evidence for linkage of DHS to microsatellite markers on the long arm of chromosome 16 (16q23-q24). A maximum two-point LOD score of 6.62 at recombination fraction .00 was obtained with marker D16S520. There are no recombination events defining the telomeric limit of the region, which therefore is quite large. No candidate genes map to this area.