October 31, 2019
Twitter Poll: October 30, 2019
- Published: October 31, 2019
- By: Vanessa Moreno, MD
ADPKD is genetically heterogeneous with two major genes, PKD1 and PKD2 (~90% families), and a rare third locus, GANAB lately discovered. Less than 10% of ADPKD families are negative for these genes. More recently, DNAJB11 has been identified in those patients from ADPKD-negative pedigrees.
For the blog:
ADPKD is the most common inherited kidney disorder. Two genes PKD1 and PKD2, coding for membrane proteins involved in the primary cilium, account for more than 90% of typical cases of ADPKD. A third gene, GANAB coding for the α-subunit of the endoplasmic reticulum-resident enzyme glucosidase II, has been associated with ADPKD and liver disease. Less than 10% of ADPKD families are negative for these 3 genes.
More recently, Cornec-Le Gall and colleagues identified a missense variant and a frameshifting change in DNAJB11 in affected individuals from two negative ADPKD-negative pedigrees. These patients presented with nonenlarged polycystic kidney and liver cysts. DNAJB11 enocdes for a cofactor of the heat shock 70 kDa (HSP70) chaperone binding immunoglobulin protein (AKA GRP-78), which regulates the folding, oligomerization, trafficking, and degradation of proteins in the lumen of the endoplasmic reticulum.
Cornec-Le Gall E., Torres VE and Harris PC. Genetic Complexitiy of Autosomal Dominant Polycystic Kidney and Liver Disease. JASN 2018; 29:13-23.
Cornec-Le Gall E., et al. Monoallelic Mutations to DNAJB11 Cause Atypical Autosomal-Dominant Polycystic Kidney Disease. Am J Hum Genet 2018; 3;102 (5):832-844.
Allison, S.J. DNAJB11: another player in ADPKD. Nat Rev Nephrol 2018; 14:476.