Inheritance of a stable mutation in a family with early-onset disease.
Autosomal/dominant polycystic kidney disease (ADPKD) exhibits a high inter- and intrafamilial heterogeneity partly explained by the involvement of at least 3 different genes in the disorder transmission. PKD1, the major locus, is located on chromosome 16p. The occurrence of very early-onset cases of ADPKD (sometimes in utero) in a few PKD1 families or the increased severity of the disease in successive generations raise the question of anticipation. This is a subject of controversial discussion. This report deals with the molecular analysis in families with very early-onset ADPKD. The finding of the same stable mutation with such different phenotypes rules out a dynamic mutation. The molecular basis of severe childhood PKD in typical ADPKD families remains unclear; it may include segregation of modifying genes or unidentified factors and the two-hit mechanism.
Perrichot
R A
RA
Service de Néphrologie, CHU Brest, France. regine.perrichot@univ-brest.fr
Mercier
B
B
de Parscau
L
L
Simon
P M
PM
Cledes
J
J
Ferec
C
C
D000328:Adult; D017668:Age of Onset; D001483:Base Sequence; D004251:DNA Transposable Elements; D005091:Exons; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D050396:TRPP Cation Channels; D013941:Thymine
D004251:DNA Transposable Elements; D011506:Proteins; D050396:TRPP Cation Channels; D013941:Thymine