Phenotypic Spectrum of Children with Nephronophthisis and Related Ciliopathies
Standard
Phenotypic Spectrum of Children with Nephronophthisis and Related Ciliopathies. / König, Jens; Kranz, Birgitta; König, Sabine; Schlingmann, Karl Peter; Titieni, Andrea; Tönshoff, Burkhard; Habbig, Sandra; Pape, Lars; Häffner, Karsten; Hansen, Matthias; Büscher, Anja; Bald, Martin; Billing, Heiko; Walden, Ulrike; Hampel, Tobias; Staude, Hagen; Riedl, Magdalena; Gretz, Norbert; Lablans, Martin; Bergmann, Carsten; Hildebrandt, Friedhelm; Omran, Heymut; Konrad, Martin; Gesellschaft für Pädiatrische Nephrologie (GPN).
In: Clinical journal of the American Society of Nephrology : CJASN, Vol. 12, No. 12, 07.12.2017, p. 1974-1983.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Phenotypic Spectrum of Children with Nephronophthisis and Related Ciliopathies
AU - König, Jens
AU - Kranz, Birgitta
AU - König, Sabine
AU - Schlingmann, Karl Peter
AU - Titieni, Andrea
AU - Tönshoff, Burkhard
AU - Habbig, Sandra
AU - Pape, Lars
AU - Häffner, Karsten
AU - Hansen, Matthias
AU - Büscher, Anja
AU - Bald, Martin
AU - Billing, Heiko
AU - Walden, Ulrike
AU - Hampel, Tobias
AU - Staude, Hagen
AU - Riedl, Magdalena
AU - Gretz, Norbert
AU - Lablans, Martin
AU - Bergmann, Carsten
AU - Hildebrandt, Friedhelm
AU - Omran, Heymut
AU - Konrad, Martin
AU - Gesellschaft für Pädiatrische Nephrologie (GPN)
N1 - Copyright © 2017 by the American Society of Nephrology.
PY - 2017/12/7
Y1 - 2017/12/7
N2 - BACKGROUND AND OBJECTIVES: Genetic heterogeneity and phenotypic variability are major challenges in familial nephronophthisis and related ciliopathies. To date, mutations in 20 different genes (NPHP1to-20) have been identified causing either isolated kidney disease or complex multiorgan disorders. In this study, we provide a comprehensive and detailed characterization of 152 children with a special focus on extrarenal organ involvement and the long-term development of ESRD.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We established an online-based registry (www.nephreg.de) to assess the clinical course of patients with nephronophthisis and related ciliopathies on a yearly base. Cross-sectional and longitudinal data were collected. Mean observation time was 7.5±6.1 years.RESULTS: In total, 51% of the children presented with isolated nephronophthisis, whereas the other 49% exhibited related ciliopathies. Monogenetic defects were identified in 97 of 152 patients, 89 affectingNPHPgenes. Eight patients carried mutations in other genes related to cystic kidney diseases. A homozygousNPHP1deletion was, by far, the most frequent genetic defect (n=60). We observed a high prevalence of extrarenal manifestations (23% [14 of 60] for theNPHP1group and 66% [61 of 92] for children withoutNPHP1). A homozygousNPHP1deletion not only led to juvenile nephronophthisis but also was able to present as a predominantly neurologic phenotype. However, irrespective of the initial clinical presentation, the kidney function of all patients carryingNPHP1mutations declined rapidly between the ages of 8 and 16 years, with ESRD at a mean age of 11.4±2.4 years. In contrast within the non-NPHP1group, there was no uniform pattern regarding the development of ESRD comprising patients with early onset and others preserving normal kidney function until adulthood.CONCLUSIONS: Mutations inNPHPgenes cause a wide range of ciliopathies with multiorgan involvement and different clinical outcomes.
AB - BACKGROUND AND OBJECTIVES: Genetic heterogeneity and phenotypic variability are major challenges in familial nephronophthisis and related ciliopathies. To date, mutations in 20 different genes (NPHP1to-20) have been identified causing either isolated kidney disease or complex multiorgan disorders. In this study, we provide a comprehensive and detailed characterization of 152 children with a special focus on extrarenal organ involvement and the long-term development of ESRD.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We established an online-based registry (www.nephreg.de) to assess the clinical course of patients with nephronophthisis and related ciliopathies on a yearly base. Cross-sectional and longitudinal data were collected. Mean observation time was 7.5±6.1 years.RESULTS: In total, 51% of the children presented with isolated nephronophthisis, whereas the other 49% exhibited related ciliopathies. Monogenetic defects were identified in 97 of 152 patients, 89 affectingNPHPgenes. Eight patients carried mutations in other genes related to cystic kidney diseases. A homozygousNPHP1deletion was, by far, the most frequent genetic defect (n=60). We observed a high prevalence of extrarenal manifestations (23% [14 of 60] for theNPHP1group and 66% [61 of 92] for children withoutNPHP1). A homozygousNPHP1deletion not only led to juvenile nephronophthisis but also was able to present as a predominantly neurologic phenotype. However, irrespective of the initial clinical presentation, the kidney function of all patients carryingNPHP1mutations declined rapidly between the ages of 8 and 16 years, with ESRD at a mean age of 11.4±2.4 years. In contrast within the non-NPHP1group, there was no uniform pattern regarding the development of ESRD comprising patients with early onset and others preserving normal kidney function until adulthood.CONCLUSIONS: Mutations inNPHPgenes cause a wide range of ciliopathies with multiorgan involvement and different clinical outcomes.
KW - Journal Article
U2 - 10.2215/CJN.01280217
DO - 10.2215/CJN.01280217
M3 - SCORING: Journal article
C2 - 29146700
VL - 12
SP - 1974
EP - 1983
JO - CLIN J AM SOC NEPHRO
JF - CLIN J AM SOC NEPHRO
SN - 1555-9041
IS - 12
ER -
