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
disorder characterized by salt-wasting in infancy arising from
target organ unresponsiveness to mineralocorticoids. Clinical
expression of the disease varies from severely affected infants who
may die to apparently asymptomatic individuals. Inheritance is
Mendelian and may be either autosomal dominant or autosomal
recessive. A defect in the mineralocorticoid receptor has been
implicated as a likely cause of PHA1. The gene for human
mineralocorticoid receptor (MLR) has been cloned and physically
mapped to human chromosome 4q31.1-31.2. The etiological role of MLR
in autosomal recessive PHA1 was investigated by performing linkage
analysis between PHA1 and three simple sequence length
polymorphisms (D4S192, D4S1548, and D4S413) on chromosome 4q in 10
consanguineous families. Linkage analysis was carried out assuming
autosomal recessive inheritance with full penetrance and zero
phenocopy rate using the MLINK program for two-point analysis and
the HOMOZ program for multipoint analysis. Lod scores of less than
-2 were obtained over the whole region from D4S192 to D4S413
encompassing MLR. This provdes evidence against MLR as the site of
mutations causing PHA1 in the majority of autosomal recessive
families.