EXCLUSION OF THE LOCUS FOR AUTOSOMAL RECESSIVE PSEUDOHYPOALDOSTERONISM TYPE-1 FROM THE MINERALOCORTICOID RECEPTOR GENE REGION ON HUMAN-CHROMOSOME 4Q BY LINKAGE ANALYSIS

Pseudohypoaldosteronism type 1 (PHA1) is an uncommon inherited disorde r characterized by salt-wasting in infancy arising from target organ u nresponsiveness to mineralocorticoids. Clinical expression of the dise ase varies from severely affected infants who may die to apparently as ymptomatic individuals. Inheritance is Mendelian and may be either aut osomal dominant or autosomal recessive. A defect in the mineralocortic oid receptor has been implicated as a likely cause of PHA1. The gene f or human mineralocorticoid receptor (MLR) has been cloned and physical ly mapped to human chromosome 4q31.1-31.2. The etiological role of MLR in autosomal recessive PHA1 was investigated by performing linkage an alysis between PHA1 and three simple sequence length polymorphisms (D4 S192, D4S1548, and D4S413) on chromosome 4q in 10 consanguineous famil ies. Linkage analysis was carried out assuming autosomal recessive inh eritance with full penetrance and zero phenocopy rate using the MLINK program for two-point analysis and the HOMOZ program for multipoint an alysis. Lod scores of less than -2 were obtained over the whole region from D4S192 to D4S413 encompassing MLR. This provides evidence agains t MLR as the site of mutations causing PHA1 in the majority of autosom al recessive families.