Abstract
BackgroundGenetic testing of patients with inherited kidney diseases has emerged as a tool of clinical utility by improving the patients’ diagnosis, prognosis, surveillance and therapy.MethodsThe present study applied a Next Generation Sequencing (NGS)-based panel, named NephroPlex, testing 115 genes causing renal diseases, to 119 individuals, including 107 probands and 12 relatives. Thirty-five (poly)cystic and 72 non (poly)cystic individuals were enrolled. The latter subgroup of patients included Bardet-Biedl syndrome (BBS) patients, as major components.ResultsDisease-causing mutations were identified in 51.5 and 40% of polycystic and non-polycystic individuals, respectively. Autosomal dominant polycystic kidney disease (ADPKD) patients with truncating PKD1 variants showed a trend towards a greater slope of the age-estimated glomerular filtration rate (eGFR) regression line than patients with (i) missense variants, (ii) any PKD2 mutations and (iii) no detected mutations, according to previous findings. The analysis of BBS individuals showed a similar frequency of BBS4,9,10 and 12 mutations. Of note, all BBS4-mutated patients harbored the novel c.332+1G>GTT variant, which was absent in public databases, however, in our internal database, an additional heterozygote carrier was found. All BBS4-mutated individuals originated from the same geographical area encompassing the coastal provinces of Naples.DiscussionIn conclusion, these findings indicate the potential for a genetic panel to provide useful information at both clinical and epidemiological levels.Graphic abstract
Highlights
The development of “Next-Generation Sequencing” (NGS) has determined a revolution in clinical genetics, improving the possibility of increasing sequencing content while dramatically reducing costs, due to the simultaneous analysis of multiple genes through one single reaction [1,2,3]
Probands underwent genetic analysis to address the molecular basis of the following clinical pictures: inherited polycystic diseases (N = 35) (Table 1); among non-cystic patients, the following categories were included in the study; hypokalemic metabolic alkalosis tubulopathies (n = 12), Fanconi syndrome (n = 1), cystinuria (n = 1), renal glycosuria (n = 3), distal renal tubular acidosis /dRTA (n = 2), hypercalciuria (n = 8), diabetes insipidus (n = 1), Alport Syndrome/ AS(n = 11), congenital anomalies of kidney and urinary tract (CAKUT)(N = 5), Bardet-Biedl Syndrome/ Bardet-Biedl syndrome (BBS) (n = 27), and resistant hypertension (n = 1) (Table 2)
Thirty-six variants in PKD1 and PKD2 were found in 25 individuals; twenty-two variants were novel, the remaining were already described in the literature
Summary
The development of “Next-Generation Sequencing” (NGS) has determined a revolution in clinical genetics, improving the possibility of increasing sequencing content while dramatically reducing costs, due to the simultaneous analysis of multiple genes through one single reaction [1,2,3]. We developed a gene panel that includes 115 genes causing kidney disorders, including major genetic loci which account for ~ 85–90% of ADPKD and over 96% of Bardet-Biedl syndrome (BBS), namely PKD1-2 and BBS1-15, respectively [7, 8]. Our study illustrates the potential of using Nephroplex to test GKD patients, demonstrating its utility in the molecular diagnosis of classic, challenging and genetically heterogeneous conditions, such as ADPKD and BBS and showing major challenges in PKD1 analysis. Methods The present study applied a Generation Sequencing (NGS)-based panel, named NephroPlex, testing 115 genes causing renal diseases, to 119 individuals, including 107 probands and 12 relatives. Thirty-five (poly)cystic and 72 non (poly)cystic individuals were enrolled The latter subgroup of patients included Bardet-Biedl syndrome (BBS) patients, as major components. Discussion In conclusion, these findings indicate the potential for a genetic panel to provide useful information at both clinical and epidemiological levels
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
