Clinical characteristics of HNF1B-related disorders in a Japanese population.

Abstract

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:

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:

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 m2; p = 0.0091).

CONCLUSION:

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.

• Authors: China Nagano, Naoya Morisada, Kandai Nozu, Koichi Kamei, Ryojiro Tanaka, Shoichiro Kanda, Shinichi Shiona, Yoshinori Araki, Shinichiro Ohara, Chieko Matsumura, Katsuaki Kasahara, Yukiko Mori, Akane Seo, Kenichiro Miura, Miki Washiyama, Keisuke Sugimoto, Ryoko Harada, Satoshi Tazoe, Hiroyo Kourakata, Mayumi Enseki, Daisuke Aotani, Takeshi Yamada, Nana Sakakibara, Tomohiko Yamamura, Shogo Minamikawa, Kenji Ishikura, Shuichi Ito, Motoshi Hattori, Kazumoto Iijima
• Journal: Clinical and experimental nephrology (Clin Exp Nephrol) Vol. 23 Issue 9 Pg. 1119-1129 (Sep 2019) ISSN: 1437-7799 [Electronic] Japan
• PMID: 31131422 (Publication Type: Journal Article)

Chemical References

• HNF1B protein, human
• Hepatocyte Nuclear Factor 1-beta

Topics

• Adolescent
• Adult
• Bartter Syndrome (diagnosis, genetics)
• Central Nervous System Diseases (diagnosis, genetics)
• Child
• Child, Preschool
• Chromosome Deletion
• Chromosomes, Human, Pair 17
• Comparative Genomic Hybridization
• Dental Enamel (abnormalities)
• Diabetes Mellitus, Type 2 (diagnosis, genetics)
• Disease Progression
• Gene Deletion
• Genetic Predisposition to Disease
• Hepatocyte Nuclear Factor 1-beta (genetics)
• Heredity
• Humans
• Infant
• Japan
• Kidney Diseases, Cystic (diagnosis, genetics)
• Male
• Middle Aged
• Multiplex Polymerase Chain Reaction
• Pedigree
• Phenotype
• Prognosis
• Retrospective Studies
• Risk Factors
• Urogenital Abnormalities (diagnosis, genetics)
• Vesico-Ureteral Reflux (diagnosis, genetics)