Bi-allelic pathogenic variations in DNAJB11 cause Ivemark II syndrome, a renal-hepatic-pancreatic dysplasia

Abstract

The Nijmegen Biomedical Study is a population-based cross-sectional study conducted in the eastern part of the Netherlands. As part of the overall study, we provide reference values of estimated glomerular filtration rate (GFR) for this Caucasian population without expressed risk. Age-stratified, randomly selected inhabitants received a postal questionnaire on lifestyle and medical history. In a large subset of the responders, serum creatinine was measured. The GFR was then measured using the abbreviated Modification of Diet in Renal Disease (MDRD) formula. To limit possible bias, serum creatinine was calibrated against measurements performed in the original MDRD laboratory. The study cohort included 2823 male and 3274 female Caucasian persons aged 18-90 years. A reference population of apparently healthy subjects was selected by excluding persons with known hypertension, diabetes, cardiovascular-or renal diseases. This healthy study cohort included 1660 male subjects and 2072 female subjects, of which 869 of both genders were 65 years or older. The median GFR was 85 ml/min/1.73 m 2 in 30-to 34-year-old men and 83 ml/min/1.73 m 2 in similar aged women. In these healthy persons, GFR declined approximately 0.4 ml/min/year. Our study provides age-and gender-specific reference values of GFR in a population of Caucasian persons without identifiable risk.

Biallelic Mutations in <b><i>DNAJB11</i></b>are Associated with Prenatal Polycystic Kidney Disease in a Turkish Family

“…The mutation was shown to cause tortuous primary cilia in renal tubules in the fetus. Renal and cardiac features of the fetus were smiliar to our cases; however, pancreatic and hepatic findings were not mentioned in the autopsy report [Jordan et al, 2021].…”

“…While preparing this paper, Jordan et al [2021] reported a fetus diagnosed with renal-hepatic-pancreatic dysplasia with a homozygous c.600-2A>C splice site mutation in DNAJB11. The mutation was shown to cause tortuous primary cilia in renal tubules in the fetus.…”

Targeted next‐generation sequencing in a large series of fetuses with severe renal diseases

“…Biallelic Class 4 or 5 variants were identified in NPHP3 in one case with ductal plate anomaly, in CEP290 in one case with postaxial polydactyly, in TMEM67 in one case with occipital encephalocele, and in DNAJB11 in one case with renal, hepatic, and pancreatic dysplasia that was reported elsewhere (Jordan et al, 2020).…”

Expanding the genetic landscape of oral‐facial‐digital syndrome with two novel genes

“…Heterozygous PKD1 variants are the most common cause of adult‐onset autosomal dominant polycystic kidney disease, while biallelic PKD1 variants are associated with early and potentially neonatal‐onset, severe polycystic kidney disease (Al‐Hamed et al, 2019 ; Audrézet et al, 2016 ; Durkie et al, 2021 ). Heterozygous DNAJB11 variants are associated with autosomal dominant polycystic kidney disease, while biallelic variants cause Ivemark II syndrome or renal‐hepatic‐pancreatic dysplasia syndrome (Jordan et al, 2021 ). We propose that TOPORS has similar properties, with heterozygous variants causing the milder, organ‐specific ciliopathy retinitis pigmentosa, and biallelic variants causing OFDS‐spectrum syndromic ciliopathy.…”

“…The axoneme (blue) is composed of microtubule doublets that provides structure to the cilium and also forms the framework for ciliary transport. The nucleus (orange) is an important target of ciliary signaling (EHZ) [Color figure can be viewed at wileyonlinelibrary.com]Hamed et al, 2019;Audrézet et al, 2016;Durkie et al, 2021).Heterozygous DNAJB11 variants are associated with autosomal dominant polycystic kidney disease, while biallelic variants cause Ivemark II syndrome or renal-hepatic-pancreatic dysplasia syndrome(Jordan et al, 2021). We propose that TOPORS has similar properties, with…”