{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T21:24:34Z","timestamp":1791494674889,"version":"4.3.4"},"reference-count":12,"publisher":"Oxford University Press (OUP)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,1,1]]},"abstract":"<jats:p>Background. The TTC21B gene was initially described as causative of nephronophthisis (NPHP). Recently, the homozygous TTC21B p.P209L mutation has been identified in families with focal segmental glomerulosclerosis (FSGS) and tubulointerstitial lesions. Heterozygous TTC21B variants have been proposed as genetic modifiers in ciliopathies. We aimed to study the causative and modifying role of the TTC21B gene in glomerular and cystic kidney diseases.<\/jats:p>\n                  <jats:p>Methods. Mutation analysis of the TTC21B gene was performed by massive parallel sequencing. We studied the causative role of the TTC21B gene in 17 patients with primary diagnosis of FSGS or NPHP and its modifying role in 184 patients with inherited glomerular or cystic kidney diseases.<\/jats:p>\n                  <jats:p>Results. Disease-causing TTC21B mutations were identified in three families presenting nephrotic proteinuria with FSGS and tubulointerstitial lesions in which some family members presented hypertension and myopia. Two families carried the homozygous p.P209L and the third was compound heterozygous for the p.P209L and a novel p.H426D mutation. Rare heterozygous TTC21B variants predicted to be pathogenic were found in five patients. These TTC21B variants were significantly more frequent in renal patients compared with controls (P = 0.0349). Two patients with a heterozygous deleterious TTC21B variant in addition to the disease-causing mutation presented a more severe phenotype than expected.<\/jats:p>\n                  <jats:p>Conclusions. Our results confirm the causal role of the homozygous p.P209L TTC21B mutation in two new families with FSGS and tubulointerstitial disease. We identified a novel TTC21B mutation demonstrating that p.P209L is not the unique causative mutation of this nephropathy. Thus, TTC21B mutation analysis should be considered for the genetic diagnosis of families with FSGS and tubulointerstitial lesions. Finally, we provide evidence that heterozygous deleterious TTC21B variants may act as genetic modifiers of the severity of glomerular and cystic kidney diseases.<\/jats:p>","DOI":"10.1093\/ndt\/gfv453","type":"journal-article","created":{"date-parts":[[2016,3,3]],"date-time":"2016-03-03T20:55:10Z","timestamp":1457038510000},"page":"151-156","source":"Crossref","is-referenced-by-count":20,"title":["Contribution of the\n                    <i>TTC21B<\/i>\n                    gene to glomerular and cystic kidney diseases"],"prefix":"10.1093","volume":"32","author":[{"given":"Gemma","family":"Bullich","sequence":"first","affiliation":[{"name":"1Molecular Biology Laboratory, Fundaci\u00f3 Puigvert, Instituto de Investigaciones Biom\u00e9dicas Sant Pau (IIB-Sant Pau), Universitat Aut\u00f2noma de Barcelona, REDinREN, Instituto de Investigaci\u00f3n Carlos III, Barcelona, Catalonia, Spain"},{"name":"2Nephrology Department, Fundaci\u00f3 Puigvert, Instituto de Investigaciones Biom\u00e9dicas Sant Pau (IIB-Sant Pau), Universitat Aut\u00f2noma de Barcelona, REDinREN, Instituto de Investigaci\u00f3n Carlos III, Barcelona, Catalonia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iv\u00e1n","family":"Vargas","sequence":"additional","affiliation":[{"name":"3Informatics Department, Institut de diagn\u00f2stic per la imatge (IDI), Barcelona, Catalonia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Trujillano","sequence":"additional","affiliation":[{"name":"4Genomics and Disease Group, Bioinformatics and Genomics Programme, Centre for Genomic Regulation (CRG), Barcelona, Catalonia, Spain"},{"name":"5Universitat Pompeu Fabra, Barcelona, Catalonia, Spain"},{"name":"6Hospital del Mar Medical Research Institute (IMIM), Barcelona, Catalonia, Spain"},{"name":"7CIBER in Epidemiology and Public Health (CIBERESP), Barcelona, Catalonia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santiago","family":"Mendiz\u00e1bal","sequence":"additional","affiliation":[{"name":"8Pediatric Nephrology Department, Hospital Universitario La Fe, Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Alberto","family":"Pi\u00f1ero-Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"9Pediatric Nephrology Department, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Fraga","sequence":"additional","affiliation":[{"name":"10Pediatric Nephrology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Catalonia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Garc\u00eda-Solano","sequence":"additional","affiliation":[{"name":"11Pathology Service, Hospital General Universitario Santa Luc\u00eda, Cartagena, 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