Phenotypic differences and similarities of monozygotic twins with maturity‐onset diabetes of the young type 5

Ohara, Yasuko; Okada, Yuko; Yamada, Tomoko; Sugawara, Kenji; Kanatani, Masayuki; Fukuoka, Hidenori; Maeda, Toshiro; Morisada, Naoya; Iijima, Kazumoto; Ogawa, Wataru

doi:10.1111/jdi.13004

Cited by 7 publications

(6 citation statements)

References 12 publications

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“…We would like to thank Editage (www.editage.jp) for English language editing. Data for SC57, SC226, SC292, SC376, and SC412 patients were published elsewhere [9,22,23].…”

Section: Acknowledgmentsmentioning

confidence: 99%

Clinical characteristics of HNF1B-related disorders in a Japanese population

et al. 2019

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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 6 the patients with heterozygous variants compared to those in patients harboring the deletion (median: 37.6 vs 58.8 ml/min/1.73 m ; 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.

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“…We would like to thank Editage (www.editage.jp) for English language editing. Data for SC57, SC226, SC292, SC376, and SC412 patients were published elsewhere [9,22,23].…”

Section: Acknowledgmentsmentioning

confidence: 99%

Clinical characteristics of HNF1B-related disorders in a Japanese population

et al. 2019

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“…However, they displayed different renal and pancreatic manifestations: one had severely impaired endogenous insulin secretion and mild renal dysfunction, while the other had severe renal dysfunction and relatively preserved endogenous insulin secretion. [ 22 ] Thus, slight differences in genetic information observed in monozygotic twins, such as those in mitochondrial DNA and DNA methylation, may affect the phenotypic manifestation of MODY 5.…”

Section: Discussionmentioning

confidence: 99%

Maturity-Onset diabetes of the young type 5 treated with the glucagon-like peptide-1 receptor agonist

et al. 2020

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Rationale: Maturity-onset diabetes of the young type 5 (MODY 5) is a form of monogenic diabetes that is often accompanied by pancreatic dysfunction. To date, no cases of MODY 5 treated with glucagon-like peptide-1 receptor agonist (GLP-1RA) have been reported. We present the first case of MODY 5 treated with GLP-1RA. Patient concerns: A 17-year-old woman, with a history of being operated for congenital ileal atresia at birth, was admitted to our hospital due to hyperglycemia. She had been clinically diagnosed with type 1 diabetes 1 month prior, and administered 14 units of insulin glargine 300 U/mL per day. Diagnosis: She had hypopotassemia, hypomagnesaemia, pancreatic body, and tail defects, multiple renal cysts, and a family history of diabetes, and urogenital anomaly. Genetic testing revealed heterozygous deletion of hepatocyte nuclear transcription factor-1 beta, leading to the diagnosis of MODY 5. Interventions: The patient was treated with multiple daily insulin injections for 9 days (22 units/d) before administration of GLP-1RA, and then liraglutide was initiated. Outcomes: Liraglutide treatment (0.6 mg/d) alone maintained the patient's glycated hemoglobin level below 7.0% for at least 12 months after discharge. A higher dose, 0.9 mg/d, of liraglutide was not tolerated by the patient due to nausea. Serum levels of C-peptide immunoreactivity were 1.15 ng/mL and 1.91 ng/mL, respectively, after 6 and 12 months of liraglutide therapy. Lessons: GLP-1RA might be effective at regulating glucose metabolism by utilizing residual pancreatic endocrine function in patients with MODY 5. Imaging and genetic screening were helpful in the diagnosis of MODY 5.

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“…Nevertheless, no other illnesses or health problems were found. To elucidate the various clinical presentations and characteristics of Chr17 deletion, we compared the clinical manifestations in our proband and previously reported patients with a similar deletion region (34,437.475-36,424,950) in Chr17q12 [7][8][9][10][11][12][13][14][15] (Fig. 2, Table 1).…”

Section: Case Presentationmentioning

confidence: 99%

“…Even between parents and children without differences in the deletion region, the significant variance in clinical phenotypes is presented [7,11,13]. Likewise, the severity of renal and pancreatic defects varied between monozygotic twins with MODY5 due to Chr17q12 deletion [8].…”

Section: Case Presentationmentioning

confidence: 99%

A rare combination of MODY5 and duodenal atresia in a patient: a case report

Zeng

Wen

et al. 2020

BMC Med Genet

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Background: Maturity-onset diabetes of the young (MODY) is a genetically and clinically heterogeneous group of hereditary diabetes, generally caused by one abnormal gene. MODY5 is caused by mutations of the hepatocyte nuclear factor 1 homeobox β gene (HNF1β), always as a part of Chr17q12 deletion, whereas heterozygous mutation in B lymphocyte kinase (BLK) gene is responsible for MODY11. Case presentation: We report a patient who developed diabetes with a 1.58-Mb Chr17q12 microdeletion and BLK gene c.211G > A mutation using the cytoscan high-density array and whole-exome sequencing analysis. The patient received the surgery at five days after birth for the duodenal atresia and had normal growth postoperatively. Mild elevated liver enzymes were found along with the normal renal function. Quantitative analysis of β-cell function markers, including fasting insulin (< 0.2 mIU/L), fasting C-peptide (0.02 μg/L), postprandial-2 h insulin (< 0.2 mIU/L), and postprandial-2 h C-peptide (0.03 μg/L) suggested a severe loss of insulin secreting capacity. Meanwhile, islet autoantibodies (GADA, IA-2, ICA, and IAA) in the patient's blood appeared negative. Neither dysplasia in other tissues nor abnormality in development and behavior was found. Conclusion: To date, gastrointestinal malformations were extremely rarely reported in patients with MODY. Our clinical report further expands the clinical presentation and variability of MODY5.

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Phenotypic differences and similarities of monozygotic twins with maturity‐onset diabetes of the young type 5

Cited by 7 publications

References 12 publications

Clinical characteristics of HNF1B-related disorders in a Japanese population

Clinical characteristics of HNF1B-related disorders in a Japanese population

Maturity-Onset diabetes of the young type 5 treated with the glucagon-like peptide-1 receptor agonist

A rare combination of MODY5 and duodenal atresia in a patient: a case report

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