scholarly journals Autosomal dominant tubulointerstitial kidney disease genotype and phenotype correlation in a Chinese cohort

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kunjing Gong ◽  
Min Xia ◽  
Yaqin Wang ◽  
Na Wang ◽  
Ying Liu ◽  
...  
Keyword(s):  
Amino Acid ◽  
Kidney Disease ◽  
Autosomal Dominant ◽  
Copy Number Variations ◽  
Single Nucleotide Variants ◽  
Pathogenic Variants ◽  
Screening Study ◽  
Chinese Cohort ◽  
Combination Of Methods

AbstractGenes of UMOD, HNF1B, MUC1, REN and SEC61A1 were reported to be associated with autosomal dominant tubulointerstitial kidney disease (ADTKD). 48 probands and their family members (N = 27) were enrolled in this genetic screening study. A combination of methods was employed for comprehensive molecular analysis of both copy number variations (CNVs) and single nucleotide variants (SNVs). 35 probands were followed for years. The phenotype-genotype and genotype-outcome correlation were inferred from these datasets. In this cohort, 18 probands were diagnosed with ADTKD, according to Kidney Disease: Improving Global Outcomes (KDIGO) guideline. Moreover, 11 probands were diagnosed with ADTKD-UMOD, one with ADTKD-REN and one with ADTKD-HNF1B, based on molecularly confirmed pathogenic variants. The 11 UMOD variants were mainly located in codons 28 to 289 and half of the variants were found to change the cysteine amino acid. According to the follow-up data, suspected ADTKD individuals had a better prognosis compared to ADTKD individuals (p = 0.029). Individuals with a cysteine substitution in the UMOD gene appeared to have a better prognosis than individuals with other amino acid substitutions (p = 0.015).

scholarly journals Unsuspected somatic mosaicism for FBN1 gene contributes to Marfan syndrome

2021 ◽  
Author(s):  
Pauline Arnaud ◽  
Hélène Morel ◽  
Olivier Milleron ◽  
Laurent Gouya ◽  
Christine Francannet ◽  
...  
Keyword(s):  
Marfan Syndrome ◽  
Somatic Mosaicism ◽  
Variant Calling ◽  
Copy Number Variations ◽  
Pathogenic Variant ◽  
Single Nucleotide Variants ◽  
Bioinformatics Analyses ◽  
Single Nucleotide ◽  
Fbn1 Gene ◽  
Pathogenic Variants

Abstract Purpose Individuals with mosaic pathogenic variants in the FBN1 gene are mainly described in the course of familial screening. In the literature, almost all these mosaic individuals are asymptomatic. In this study, we report the experience of our team on more than 5,000 Marfan syndrome (MFS) probands. Methods Next-generation sequencing (NGS) capture technology allowed us to identify five cases of MFS probands who harbored a mosaic pathogenic variant in the FBN1 gene. Results These five sporadic mosaic probands displayed classical features usually seen in Marfan syndrome. Combined with the results of the literature, these rare findings concerned both single-nucleotide variants and copy-number variations. Conclusion This underestimated finding should not be overlooked in the molecular diagnosis of MFS patients and warrants an adaptation of the parameters used in bioinformatics analyses. The five present cases of symptomatic MFS probands harboring a mosaic FBN1 pathogenic variant reinforce the fact that apparently asymptomatic mosaic parents should have a complete clinical examination and a regular cardiovascular follow-up. We advise that individuals with a typical MFS for whom no single-nucleotide pathogenic variant or exon deletion/duplication was identified should be tested by NGS capture panel with an adapted variant calling analysis.

scholarly journals Genotype-Phenotype Correlations in Neurofibromatosis Type 1: A Single-Center Cohort Study

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1879
Author(s):  
Marcello Scala ◽  
Irene Schiavetti ◽  
Francesca Madia ◽  
Cristina Chelleri ◽  
Gianluca Piccolo ◽  
...  
Keyword(s):  
Neurofibromatosis Type 1 ◽  
Neurofibromatosis Type ◽  
Copy Number Variations ◽  
Single Nucleotide Variants ◽  
Multivariate Statistical ◽  
Gene Deletions ◽  
Pathogenic Variants ◽  
Lisch Nodules ◽  
Next Generation Sequencing Ngs

Neurofibromatosis type 1 (NF1) is a proteiform genetic condition caused by pathogenic variants in NF1 and characterized by a heterogeneous phenotypic presentation. Relevant genotype–phenotype correlations have recently emerged, but only few pertinent studies are available. We retrospectively reviewed clinical, instrumental, and genetic data from a cohort of 583 individuals meeting at least 1 diagnostic National Institutes of Health (NIH) criterion for NF1. Of these, 365 subjects fulfilled ≥2 NIH criteria, including 235 pediatric patients. Genetic testing was performed through cDNA-based sequencing, Next Generation Sequencing (NGS), and Multiplex Ligation-dependent Probe Amplification (MLPA). Uni- and multivariate statistical analysis was used to investigate genotype–phenotype correlations. Among patients fulfilling ≥ 2 NIH criteria, causative single nucleotide variants (SNVs) and copy number variations (CNVs) were detected in 267/365 (73.2%) and 20/365 (5.5%) cases. Missense variants negatively correlated with neurofibromas (p = 0.005). Skeletal abnormalities were associated with whole gene deletions (p = 0.05) and frameshift variants (p = 0.006). The c.3721C>T; p.(R1241*) variant positively correlated with structural brain alterations (p = 0.031), whereas Lisch nodules (p = 0.05) and endocrinological disorders (p = 0.043) were associated with the c.6855C>A; p.(Y2285*) variant. We identified novel NF1 genotype–phenotype correlations and provided an overview of known associations, supporting their potential relevance in the implementation of patient management.

scholarly journals Long-Term Outcomes in Patients with Very-Early Onset Autosomal Dominant Polycystic Kidney Disease

2016 ◽  
Vol 44 (3) ◽  
pp. 171-178 ◽  
Author(s):  
Kristen L. Nowak ◽  
Melissa A. Cadnapaphornchai ◽  
Michel B. Chonchol ◽  
Robert W. Schrier ◽  
Berenice Gitomer
Keyword(s):  
Kidney Disease ◽  
Clinical Outcomes ◽  
Polycystic Kidney Disease ◽  
Early Onset ◽  
Autosomal Dominant ◽  
Glomerular Hyperfiltration ◽  
Polycystic Kidney ◽  
Autosomal Dominant Polycystic Kidney

Background: Long-term clinical outcomes in children with very-early onset (VEO; diagnosis in utero or within the first 18 months of life) autosomal dominant polycystic kidney disease (ADPKD) are currently not well understood. We conducted a longitudinal retrospective cohort study to assess the association between VEO status and adverse clinical outcomes. Methods: Seventy patients with VEO-ADPKD matched (by year of birth, sex and race/ethnicity) to 70 patients with non-VEO-ADPKD who participated in research at the University of Colorado were studied. Kaplan-Meier survival analysis was performed. The predictor was VEO status, and outcomes were progression to end-stage renal disease (ESRD), development of hypertension, progression to estimated glomerular filtration rate (eGFR <90 ml/min/1.73 m2), glomerular hyperfiltration (eGFR ≥140 ml/min/1.73 m2) and height-adjusted total kidney volume (htTKV) measured by MRI ≥600 ml/m. Results: Median follow-up was until 16.0 years of age. There were only 4 ESRD events during the follow-up period, all in the VEO group (p < 0.05). VEO patients were more likely to develop hypertension (hazard ratio, HR 3.15, 95% CI 1.86-5.34; p < 0.0001) and to progress to eGFR <90 ml/min/1.73 m2 (HR 1.97, 95% CI 1.01-3.84; p < 0.05) than non-VEO patients. There was no difference between groups in the development of glomerular hyperfiltration (HR 0.89, 95% CI 0.56-1.42; p = 0.62). There were only 7 patients who progressed to htTKV ≥600 ml/m, 4 in the VEO group and 3 in the non-VEO group (p < 0.01). Conclusions: Several clinical outcomes are worse in patients with VEO-ADPKD compared to non-VEO ADPKD. Children with VEO-ADPKD represent a particularly high-risk group of ADPKD patients.

P0708ASSOCIATION OF OBESITY WITH KIDNEY CYST GROWTH IN PATIENTS WITH AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE; RESULTS FROM KNOW-CKD COHORT DATA

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Chang Seong Kim ◽  
Hong Sang Choi ◽  
Eun hui Bae ◽  
Seong Kwon Ma ◽  
Soo Wan Kim
Keyword(s):  
Body Mass Index ◽  
Body Weight ◽  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Body Mass ◽  
Autosomal Dominant ◽  
Obese Patients ◽  
Polycystic Kidney ◽  
Autosomal Dominant Polycystic Kidney

Abstract Background and Aims Overweight or obese patients with autosomal dominant polycystic kidney disease (ADPKD) are associated with the decline of glomerular filtration rate. However, little is known about the annual rate of change in total kidney volume (TKV) in patients with ADPKD according to the body mass index (BMI) corrected by TKV and total liver volume (TLV). Method We analyzed 364 patients with ADPKD from the KoreaN Cohort Study for Outcomes in Patients with Chronic Kidney Disease. We compared the changes in TKV in less than 1-year, 2-years and 4-year follow-up from patients by dividing baseline body mass index (BMI) by 18.5 to 22.9 (normal), 23 to 24.9 (overweight), and &gt; 25 kg/m2 (obesity). Results During the 4-year follow-up period, TKV tended to increase statistically with increasing BMI (P = 0.032). Similarly, higher BMI group showed higher TKV than lower BMI group (P = 0.016). Conventional BMI is affected by TKV and TLV in advanced ADPKD patients. Therefore, we reclassified patients by corrected BMI using the adjusted body weight (body weight – TKV – TLV). Although the statistical significances between absolute value of TKV and corrected BMI groups were disappeared during the follow-up, TKV% change/year showed significantly higher in ADPKD patients with obesity among corrected BMI groups (normal; 20.2%, overweight; 17.6% and obesity; 30.6%, P for trend = 0.022) Conclusion Even after correcting the TKV and TVL, obese patients showed a high of TKV% change/year compared to non-obese patients with ADPKD.

scholarly journals Determinants and Incidence of Chronic Kidney Disease on Tenofovir-Based Antiretroviral Therapy Regimens: A Cohort Study in HIV-Infected Adults in South China

2021 ◽  
Author(s):  
Fang Liu ◽  
Hong Liu ◽  
Chen Chen ◽  
Liang-bin Miao ◽  
Zhao-yi Li ◽  
...  
Keyword(s):  
Risk Factors ◽  
Chronic Kidney Disease ◽  
Viral Load ◽  
Kidney Disease ◽  
Renal Dysfunction ◽  
Multiple Imputation ◽  
Estimating Equation ◽  
Chinese Cohort ◽  
Hiv 1

Abstract Background: To evaluate the incidence and risk factors of stage 3 chronic kidney disease (CKD) and rapid kidney function decline (RKFD) among Chinese HIV-1 infected patients starting with tenofovir (TDF)-based regimen.Methods: We enrolled in 797 TDF-initiated HIV-1-infected patients in a Chinese cohort. Kidney dysfunction were defined as stage 3 CKD (eGFR < 60 mL/min/1.73 m2 during follow-up) and RKFD (eGFR decline > 10 mL/min/1.73 m2/year). A linear mixed-effects model was used to quantify the average eGFR change per 48 weeks. A generalized estimating equation regression analysis was conducted to determine the risk factors associated with renal dysfunction. The method of multiple imputation was used to reduce bias caused by missing data.Results: In this retrospective study, 14 (2%) patients experienced stage 3 CKD, and 272 (34%) individuals experienced RKFD during a median of 26 (IQR, 4-78; maximum 325) weeks follow-up period. The mean loss in eGFR per 48 weeks increased consistently over time, from -2.59 mL/min/1.73 m2 before 48 weeks to -17.61 mL/min/1.73 m2 after 288 weeks. For every 10 mL/min/1.73 m2 increase of eGFR, the risk of RKFD increased by 29% (95%CI: 18%, 40%). Each 10 years older and every 10 mL/min/1.73 m2 higher in baseline eGFR, the risk of stage 3 CKD increased to 1.56 (95% CI: 1.00, 2.43) and decreased by 65% (95% CI: 48%, 76%), respectively. Anemia and higher viral load were significantly associated with RKFD. The results were robust across a range of multiple imputation analysis.Conclusions: TDF-associated CKD is rare in HIV-1 infected Chinese adults. Longer TDF-exposed patients are more likely to have renal dysfunction, especially those with older age, anemia, lower baseline eGFR and higher viral load.

scholarly journals Evolution of metabolic syndrome components in patients with autosomal-dominant polycystic kidney disease: a six-year follow-up study

2019 ◽  
Vol 73 ◽  
pp. 598-607
Author(s):  
Maria Pietrzak-Nowacka ◽  
Krzysztof Safranow ◽  
Małgorzata Marchelek-Myśliwiec ◽  
Mariusz Bodnar ◽  
Sylwia Przysiecka ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Renal Function ◽  
Uric Acid ◽  
Kidney Disease ◽  
Autosomal Dominant ◽  
Polycystic Kidney ◽  
Autosomal Dominant Polycystic Kidney

Aim: Long-term studies show that some metabolic syndrome (MS) components deteriorate renal function in autosomal dominant polycystic kidney disease (ADPKD) patients. The aim of this 6-year follow-up was to analyze early changes of all MS components and their associations with kidney function in the nondiabetic ADPKD patients with normal renal function, compared to controls. Material/Methods: The follow-up physical and laboratory examinations were performed for 39 ADPKD patients (age 43.7 ± 11.4 years) and 44 controls (43.5 ± 9.1 years). Results: We noticed a significant increase in weight, body mass index (BMI), waist, total and LDL cholesterol, C-peptide, uric acid, creatinine and significant decline of HbA1c and e-GFR in the ADPKD group. Increases in waist, uric acid and creatinine concentrations were significantly higher in the ADPKD patients than controls. Both groups showed similar rates of prediabetes, while diabetes developed in 5 controls (with 4 cases of type 2 diabetes and one case of type 1), but not in the ADPKD group (11% vs 0%, P = 0.06 for diabetes, 9% vs 0%, P = 0.12 for type 2 diabetes). The ADPKD group showed a significantly higher percentage of obesity, waist circumferences, systolic/diastolic blood pressure, concentrations of creatinine, urea and uric acid and lower e-GFR. The MS prevalence was comparable; however, the number of MS components was significantly higher in the ADPKD patients (median 2 vs. 1, p = 0.001). Conclusions: The presence of MS does not influence the rate of renal failure progression in nondiabetic ADPKD patients with normal renal function at a 6-year follow-up.

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