Gribouval O et al. (2005) Mutations in genes in the renin-angiotensin system are associated with autosomal recessive renal tubular dysgenesis. Nat Genet 37: 964–968

According to a recent study, genetic defects in the renin–angiotensin system (RAS) are linked to, and could be the fundamental cause of, autosomal recessive renal tubular dysgenesis (RTD), a severe fetal disorder of kidney development associated with anuria, hypotension and perinatal death. This important discovery might eventually aid early prenatal diagnosis and present genetic counseling opportunities for affected families.

Gribouval et al. analyzed the kidneys of 16 deceased fetuses and neonates with RTD, from nine families (five with a common bloodline). There was an absence of renin RNA or protein expression in three families and enhanced expression in six. All kidneys had limited differentiation of proximal tubules.

Linkage analyses and mutation screening revealed abnormalities in the genes encoding renin, angiotensinogen, angiotensin-converting enzyme or angiotensin II receptor type I. Interestingly, in one family, no mutations of RAS genes were detected, indicating that other genetic factors might also be involved in RTD.

All components of RAS are vital for the vasoconstrictor action of angiotensin II. Loss of vasocontriction would lead to chronic low perfusion pressure in the fetal kidney, and the authors propose that this is the mechanism connecting RAS gene mutations to RTD.