Clinical characteristics of HNF1B-related disorders in a Japanese population.
Adolescent
Adult
Bartter Syndrome
/ diagnosis
Central Nervous System Diseases
/ diagnosis
Child
Child, Preschool
Chromosome Deletion
Chromosomes, Human, Pair 17
Comparative Genomic Hybridization
Dental Enamel
/ abnormalities
Diabetes Mellitus, Type 2
/ diagnosis
Disease Progression
Gene Deletion
Genetic Predisposition to Disease
Hepatocyte Nuclear Factor 1-beta
/ genetics
Heredity
Humans
Infant
Japan
Kidney Diseases, Cystic
/ diagnosis
Male
Middle Aged
Multiplex Polymerase Chain Reaction
Pedigree
Phenotype
Prognosis
Retrospective Studies
Risk Factors
Urogenital Abnormalities
/ diagnosis
Vesico-Ureteral Reflux
/ diagnosis
Diabetes
Gout
HNF1B
Hypomagnesaemia
Liver abnormality
Renal malformations
Journal
Clinical and experimental nephrology
ISSN: 1437-7799
Titre abrégé: Clin Exp Nephrol
Pays: Japan
ID NLM: 9709923
Informations de publication
Date de publication:
Sep 2019
Sep 2019
Historique:
received:
28
02
2019
accepted:
07
05
2019
pubmed:
28
5
2019
medline:
11
2
2020
entrez:
28
5
2019
Statut:
ppublish
Résumé
Hepatocyte nuclear factor 1β (HNF1B), located on chromosome 17q12, causes renal cysts and diabetes syndrome (RCAD). Moreover, various phenotypes related to congenital anomalies of the kidney and urinary tract (CAKUT) or Bartter-like electrolyte abnormalities can be caused by HNF1B variants. In addition, 17q12 deletion syndrome presents with multi-system disorders, as well as RCAD. As HNF1B mutations are associated with different phenotypes and genotype-phenotype relationships remain unclear, here, we extensively studied these mutations in Japan. We performed genetic screening of RCAD, CAKUT, and Bartter-like syndrome cases. Heterozygous variants or whole-gene deletions in HNF1B were detected in 33 cases (19 and 14, respectively). All deletion cases were diagnosed as 17q12 deletion syndrome, confirmed by multiplex ligation probe amplification and/or array comparative genomic hybridization. A retrospective review of clinical data was also conducted. Most cases had morphological abnormalities in the renal-urinary tract system. Diabetes developed in 12 cases (38.7%). Hyperuricemia and hypomagnesemia were associated with six (19.3%) and 13 cases (41.9%), respectively. Pancreatic malformations were detected in seven cases (22.6%). Ten patients (32.3%) had liver abnormalities. Estimated glomerular filtration rates were significantly lower in the patients with heterozygous variants compared to those in patients harboring the deletion (median 37.6 vs 58.8 ml/min/1.73 m We present the clinical characteristics of HNF1B-related disorders. To predict renal prognosis and complications, accurate genetic diagnosis is important. Genetic testing for HNF1B mutations should be considered for patients with renal malformations, especially when associated with other organ involvement.
Sections du résumé
BACKGROUND
BACKGROUND
Hepatocyte nuclear factor 1β (HNF1B), located on chromosome 17q12, causes renal cysts and diabetes syndrome (RCAD). Moreover, various phenotypes related to congenital anomalies of the kidney and urinary tract (CAKUT) or Bartter-like electrolyte abnormalities can be caused by HNF1B variants. In addition, 17q12 deletion syndrome presents with multi-system disorders, as well as RCAD. As HNF1B mutations are associated with different phenotypes and genotype-phenotype relationships remain unclear, here, we extensively studied these mutations in Japan.
METHODS
METHODS
We performed genetic screening of RCAD, CAKUT, and Bartter-like syndrome cases. Heterozygous variants or whole-gene deletions in HNF1B were detected in 33 cases (19 and 14, respectively). All deletion cases were diagnosed as 17q12 deletion syndrome, confirmed by multiplex ligation probe amplification and/or array comparative genomic hybridization. A retrospective review of clinical data was also conducted.
RESULTS
RESULTS
Most cases had morphological abnormalities in the renal-urinary tract system. Diabetes developed in 12 cases (38.7%). Hyperuricemia and hypomagnesemia were associated with six (19.3%) and 13 cases (41.9%), respectively. Pancreatic malformations were detected in seven cases (22.6%). Ten patients (32.3%) had liver abnormalities. Estimated glomerular filtration rates were significantly lower in the patients with heterozygous variants compared to those in patients harboring the deletion (median 37.6 vs 58.8 ml/min/1.73 m
CONCLUSION
CONCLUSIONS
We present the clinical characteristics of HNF1B-related disorders. To predict renal prognosis and complications, accurate genetic diagnosis is important. Genetic testing for HNF1B mutations should be considered for patients with renal malformations, especially when associated with other organ involvement.
Identifiants
pubmed: 31131422
doi: 10.1007/s10157-019-01747-0
pii: 10.1007/s10157-019-01747-0
doi:
Substances chimiques
HNF1B protein, human
0
Hepatocyte Nuclear Factor 1-beta
138674-15-4
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1119-1129Subventions
Organisme : The Health Labor Sciences Research Grant
ID : H24-nanchi-ippan-041
Organisme : The Health Labor Sciences Research Grant
ID : H29-nanchi-ippan-039
Organisme : Japan Society for the Promotion of Science
ID : 15K09261
Organisme : Japan Society for the Promotion of Science
ID : 18K08243
Références
J Mol Endocrinol. 2001 Aug;27(1):11-29
pubmed: 11463573
J Am Soc Nephrol. 2003 Aug;14(8):2033-41
pubmed: 12874457
EMBO J. 2004 Apr 7;23(7):1657-68
pubmed: 15029248
Ann Intern Med. 2004 Apr 6;140(7):510-7
pubmed: 15068978
J Med Genet. 2006 Jan;43(1):84-90
pubmed: 15930087
Kidney Int. 2005 Nov;68(5):1944-7
pubmed: 16221171
Nat Genet. 2006 Jan;38(1):21-3
pubmed: 16341222
Hum Mol Genet. 2006 Aug 1;15(15):2363-75
pubmed: 16801329
Diabetologia. 2008 Apr;51(4):546-53
pubmed: 18297260
J Am Soc Nephrol. 2009 May;20(5):1123-31
pubmed: 19389850
Clin J Am Soc Nephrol. 2010 Jun;5(6):1079-90
pubmed: 20378641
Clin J Am Soc Nephrol. 2013 Jul;8(7):1179-87
pubmed: 23539225
Kidney Int. 2014 Nov;86(5):1007-15
pubmed: 24897035
Nat Rev Nephrol. 2015 Feb;11(2):102-12
pubmed: 25536396
Pediatr Nephrol. 2016 May;31(5):707-14
pubmed: 26160100
J Am Soc Nephrol. 2016 Feb;27(2):345-53
pubmed: 26319241
Pediatr Transplant. 2016 May;20(3):467-71
pubmed: 26899772
Diabetes Obes Metab. 2016 Sep;18 Suppl 1:23-32
pubmed: 27615128
Diabetes Care. 2017 Nov;40(11):1436-1443
pubmed: 28420700
Clin Exp Nephrol. 2018 Aug;22(4):881-888
pubmed: 29372472
J Diabetes Investig. 2019 Jul;10(4):1112-1115
pubmed: 30637974
Pediatr Nephrol. 2019 Aug;34(8):1457-1464
pubmed: 30937553