{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T02:49:21Z","timestamp":1793155761288,"version":"4.5.0"},"reference-count":28,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2020,7,21]],"date-time":"2020-07-21T00:00:00Z","timestamp":1595289600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","award":["HI18C0013"],"award-info":[{"award-number":["HI18C0013"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>HNF1B mutations, one of the most common causes of congenital anomalies of the kidney and urinary tract, manifest as various renal and extrarenal phenotypes. We analyzed the genotype-phenotype correlations in 14 pediatric patients with HNF1B mutations. Genetic studies revealed total gene deletion in six patients (43%). All patients had bilateral renal abnormalities, primarily multiple renal cysts. Twelve patients exhibited progressive renal functional deterioration, and six of them progressed to kidney failure. The annual reduction in estimated glomerular filtration rate was\u22122.1 mL\/min\/1.73 m2. Diabetes developed in five patients (36%), including one patient with new-onset diabetes after transplantation. Neurological deficits were noted in three patients (21%), one with total gene deletion and two with missense mutations. Pancreatic abnormalities were more frequent in patients with missense mutations than in patients with other types of mutations. Genotype showed no significant correlation with renal outcomes or other extrarenal manifestations. The HNF1B scores at the times of onset and genetic diagnosis were &lt;8 in two patients and one patient, respectively. Diagnosis of HNF1B mutations is clinically difficult because of extreme phenotypic variability and incomplete penetrance. Furthermore, some phenotypes develop with age. Therefore, patient age should be taken into consideration to increase the diagnostic rate, because some phenotypes develop with age.<\/jats:p>","DOI":"10.3390\/jcm9072320","type":"journal-article","created":{"date-parts":[[2020,7,22]],"date-time":"2020-07-22T03:23:16Z","timestamp":1595388196000},"page":"2320","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Genotype and Phenotype Analyses in Pediatric Patients with HNF1B Mutations"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8327-7002","authenticated-orcid":false,"given":"Seon Hee","family":"Lim","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Seoul National University Children\u2019s Hospital, Seoul 03080, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8477-0157","authenticated-orcid":false,"given":"Ji Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Seoul National University Bundang Hospital, Seongnam 13620, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6830-7311","authenticated-orcid":false,"given":"Kyoung Hee","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Jeju National University School of Medicine, Jeju 63243, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8185-4408","authenticated-orcid":false,"given":"Yo Han","family":"Ahn","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Seoul National University Children\u2019s Hospital, Seoul 03080, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8323-5320","authenticated-orcid":false,"given":"Hee Gyung","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Seoul National University Children\u2019s Hospital, Seoul 03080, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Il-Soo","family":"Ha","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Seoul National University Children\u2019s Hospital, Seoul 03080, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7556-1265","authenticated-orcid":false,"given":"Hae Il","family":"Cheong","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Seoul National University Children\u2019s Hospital, Seoul 03080, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3553","DOI":"10.1093\/nar\/19.13.3553","article-title":"Two members of an HNF1 homeoprotein family are expressed in human liver","volume":"19","author":"Bach","year":"1991","journal-title":"Nucleic Acids Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1111\/dom.12715","article-title":"The role of hepatocyte nuclear factor 1beta in disease and development","volume":"18","author":"Vallier","year":"2016","journal-title":"Diabetes Obes. Metab."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1038\/nrneph.2014.232","article-title":"HNF1B-associated renal and extra-renal disease-an expanding clinical spectrum","volume":"11","author":"Clissold","year":"2015","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1007\/s00467-015-3142-2","article-title":"HNF1B-associated clinical phenotypes: The kidney and beyond","volume":"31","author":"Bockenhauer","year":"2016","journal-title":"Pediatr. Nephrol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.2215\/CJN.06810909","article-title":"Spectrum of HNF1B mutations in a large cohort of patients who harbor renal diseases","volume":"5","author":"Heidet","year":"2010","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1681\/ASN.2006091057","article-title":"Anomalies of the TCF2 gene are the main cause of fetal bilateral hyperechogenic kidneys","volume":"18","author":"Decramer","year":"2007","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1007\/s10157-019-01747-0","article-title":"Clinical characteristics of HNF1B-related disorders in a Japanese population","volume":"23","author":"Nagano","year":"2019","journal-title":"Clin. Exp. Nephrol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1093\/ckj\/sfy102","article-title":"Variable phenotype in HNF1B mutations: Extrarenal manifestations distinguish affected individuals from the population with congenital anomalies of the kidney and urinary tract","volume":"12","author":"Madariaga","year":"2019","journal-title":"Clin. Kidney J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1007\/s00467-011-1826-9","article-title":"HNF1B and PAX2 mutations are a common cause of renal hypodysplasia in the CKiD cohort","volume":"26","author":"Thomas","year":"2011","journal-title":"Pediatr. Nephrol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1093\/ndt\/gfu370","article-title":"Criteria for HNF1B analysis in patients with congenital abnormalities of kidney and urinary tract","volume":"30","author":"Raaijmakers","year":"2015","journal-title":"Nephrol. Dial. Transplant"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1016\/j.ekir.2019.05.019","article-title":"HNF1B mutations are associated with a gitelman-like tubulopathy that develops during childhood","volume":"4","author":"Adalat","year":"2019","journal-title":"Kidney Int. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1086\/316945","article-title":"Mutations in the hepatocyte nuclear factor-1beta gene are associated with familial hypoplastic glomerulocystic kidney disease","volume":"68","author":"Bingham","year":"2001","journal-title":"Am. J. Hum. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1038\/ki.2011.225","article-title":"Diagnosis, management, and prognosis of HNF1B nephropathy in adulthood","volume":"80","author":"Faguer","year":"2011","journal-title":"Kidney Int."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3191","DOI":"10.1002\/ajmg.a.36190","article-title":"A description of a fetal syndrome associated with HNF1B mutation and a wide intrafamilial disease variability","volume":"161A","author":"Rasmussen","year":"2013","journal-title":"Am. J. Med. Genet. A."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1038\/ki.2014.202","article-title":"The HNF1B score is a simple tool to select patients for HNF1B gene analysis","volume":"86","author":"Faguer","year":"2014","journal-title":"Kidney Int."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1681\/ASN.2008030287","article-title":"New equations to estimate GFR in children with CKD","volume":"20","author":"Schwartz","year":"2009","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"604","DOI":"10.7326\/0003-4819-150-9-200905050-00006","article-title":"A new equation to estimate glomerular filtration rate","volume":"150","author":"Levey","year":"2009","journal-title":"Ann. Intern. Med."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Ahn, Y.H., Lee, C., Kim, N.K.D., Park, E., Kang, H.G., Ha, I.S., Park, W.Y., and Cheong, H.I. (2020). Targeted exome sequencing provided comprehensive genetic diagnosis of congenital anomalies of the kidney and urinary tract. J. Clin. Med., 9.","DOI":"10.3390\/jcm9030751"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e414","DOI":"10.1038\/emm.2017.227","article-title":"Loss of podocalyxin causes a novel syndromic type of congenital nephrotic syndrome","volume":"49","author":"Kang","year":"2017","journal-title":"Exp. Mol. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American college of medical genetics and genomics and the association for molecular pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1086\/522591","article-title":"Recurrent reciprocal genomic rearrangements of 17q12 are associated with renal disease, diabetes, and epilepsy","volume":"81","author":"Mefford","year":"2007","journal-title":"Am. J. Hum. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.2337\/dc16-2462","article-title":"Diabetes, associated clinical spectrum, long-term prognosis, and genotype\/phenotype correlations in 201 adult patients with hepatocyte nuclear factor 1B (HNF1B) molecular defects","volume":"40","author":"Cornu","year":"2017","journal-title":"Diabetes Care"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1159\/000398819","article-title":"Assessment of the HNF1B score as a tool to select patients for HNF1B genetic testing","volume":"130","author":"Clissold","year":"2015","journal-title":"Nephron"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.bbrc.2010.11.108","article-title":"HNF-1B specifically regulates the transcription of the gammaa-subunit of the Na+\/K+-ATPase","volume":"404","author":"Ferre","year":"2011","journal-title":"Biochem. Biophys Res. Commun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1007\/s00467-018-4188-8","article-title":"HNF1B nephropathy has a slow-progressive phenotype in childhood-with the exception of very early onset cases: Results of the German multicenter HNF1B childhood registry","volume":"34","author":"Okorn","year":"2019","journal-title":"Pediatr. Nephrol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1681\/ASN.2008060633","article-title":"HNF1B mutations associate with hypomagnesemia and renal magnesium wasting","volume":"20","author":"Adalat","year":"2009","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1111\/petr.12690","article-title":"New-onset diabetes after renal transplantation in a patient with a novel HNF1B mutation","volume":"20","author":"Kanda","year":"2016","journal-title":"Pediatr. Transplant"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.diabet.2016.10.003","article-title":"Intellectual disability in patients with MODY due to hepatocyte nuclear factor 1B (HNF1B) molecular defects","volume":"43","author":"Charles","year":"2017","journal-title":"Diabetes Metab."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/9\/7\/2320\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:50:31Z","timestamp":1760176231000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/9\/7\/2320"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,21]]},"references-count":28,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2020,7]]}},"alternative-id":["jcm9072320"],"URL":"https:\/\/doi.org\/10.3390\/jcm9072320","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,21]]}}}