Further evidence of linkage at 7p22 with familial hyperaldosteronism type II and exclusion of genetic defects in the RBAK coding regions

Once thought rare, primary aldosteronism (PAL) is now reported to be responsible for 5–10% of hypertension. Unlike familial hyperaldosteronism type I (FH-I), FH-II is not glucocorticoidremediable and not associated with the hybrid CYP11B1/CYP11B2 gene mutation. At least five times more common than FH-I, FH-II is clinically indistinguishable from apparently sporadic PAL, suggesting an even higher incidence. Studies performed in collaboration with C Stratakis (NIH, Bethesda) on our largest Australian family (eight affected members) demonstrated linkage at chromosome 7p22. Linkage at this region was also found in a South American family (DNA provided by MI New, Mount Sinai School of Medicine, New York) and in a second Australian family. The combined multipoint LOD score for these 3 families is 4.61 (q = 0) with markers D7S462 and D7S517, providing strong support for this locus harbouring mutations responsible for FH-II. A newly identified recombination event in our largest Australian family has narrowed the region of linkage by 1.8 Mb, permitting exclusion of approximately half the genes residing in the originally reported 5 Mb linked locus. Candidate genes that are involved in cell cycle control are of interest as adrenal hyperplasia and adrenal adenomas are common in FH-II patients. A novel candidate gene in this linked region produces the retinoblastoma-associated Kruppel-associated box protein (RBaK) which interacts with the retinoblastoma gene product to repress the expression of genes activated by members of the E2F family of transcription factors.

Timber shutters, Ocean View Farmhouse, Mount Mee

Timber shutters to the living room seating alcove, in the open position.

View along North-East elevation, Ocean View Farmhouse, Mount Mee

As seen from timber entrance ramp.

North-East and North-West elevations of Ocean View Farmhouse model, Mount Mee

Cardboard the balsa model as seen from above.

Aerial view of Ocean View Farmhouse model, Mount Mee

Cardboard and balsa model as seen from above.

Living room seating alcove, Ocean View Farmhouse, Mount Mee

View of seating alcove from living room with timber shutters in the closed position.

Main deck, Ocean View Farmhouse, Mount Mee

View across main deck to farm beyond.

Living room seating alcove, Ocean View Farmhouse, Mount Mee

View to seating alcove from living room with the timber shutters in the open position.

Hand-drawn plan, Ocean View Farmhouse, Mount Mee

Plan drawing.

Leadlight windows, Ocean View Farmhouse, Mount Mee

Detailed view of leadlight windows as seen from dining room.