Searching for mutations in the HNF1B gene in a Brazilian cohort with renal cysts and hyperglycemia

Dotto, Renata Pires; Santana, Lucas Santos de; Lindsey, Susan C.; Caetano, Lílian Araújo; Franco, Luciana Ferreira; Moises, Regina Celia Mello Santiago; João, R.; Nishiura, José Luiz; Teles, Milena Gurgel; Heilberg, Ita Pfeferman; Silva, Magnus R. Dias da; Giuffrida, Fernando de Mello Almada; Reis, André

doi:10.20945/2359-3997000000138

Cited by 7 publications

(8 citation statements)

References 30 publications

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“…In a Brazilian cohort, 28 patients with clinical suspicion of HNF1B-MODY due to hyperglycemia and renal cysts were evaluated and two positive cases of HNF1B gene mutations were found. Both positive cases had a score higher than 8 [62].…”

Section: Early-onset Autosomal Dominant Diabetes Due To Hnf1a and Hnfmentioning

confidence: 87%

Update on clinical screening of maturity-onset diabetes of the young (MODY)

Peixoto-Barbosa

Reis

Giuffrida

2020

Diabetol Metab Syndr

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Background: Maturity-onset diabetes of the young (MODY) is the most common type of monogenic diabetes, being characterized by beta-cell disfunction, early onset, and autosomal dominant inheritance. Despite the rapid evolution of molecular diagnosis methods, many MODY cases are misdiagnosed as type 1 or type 2 diabetes. High costs of genetic testing and limited knowledge of MODY as a relevant clinical entity are some of the obstacles that hinder correct MODY diagnosis and treatment. We present a broad review of clinical syndromes related to most common MODY subtypes, emphasizing the role of biomarkers that can help improving the accuracy of clinical selection of candidates for molecular diagnosis. Main body: To date, MODY-related mutations have been reported in at least 14 different genes. Mutations in glucokinase (GCK), hepatocyte nuclear factor-1 homeobox A (HNF1A), and hepatocyte nuclear factor-4 homeobox A (HNF4A) are the most common causes of MODY. Accurate etiological diagnosis can be challenging. Many biomarkers such as apolipoprotein-M (ApoM), aminoaciduria, complement components, and glycosuria have been tested, but have not translated into helpful diagnostic tools. High-sensitivity C-reactive protein (hs-CRP) levels are lower in HNF1A-MODY and have been tested in some studies to discriminate HNF1A-MODY from other types of diabetes, although more data are needed. Overall, presence of pancreatic residual function and absence of islet autoimmunity seem the most promising clinical instruments to select patients for further investigation. Conclusions: The selection of diabetic patients for genetic testing is an ongoing challenge. Metabolic profiling, diabetes onset age, pancreatic antibodies, and C-peptide seem to be useful tools to better select patients for genetic testing. Further studies are needed to define cutoff values in different populations.

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Section: Early-onset Autosomal Dominant Diabetes Due To Hnf1a and Hnfmentioning

confidence: 87%

Update on clinical screening of maturity-onset diabetes of the young (MODY)

Peixoto-Barbosa

Reis

Giuffrida

2020

Diabetol Metab Syndr

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“…These authors stated, that this low prevalence of hypertension -together with the slowly progressive kidney function is the hallmark of the RCAD disease [5]. By contrast, an even smaller Brazilian study showed a prevalence of hypertension of 80% adults with RCAD syndrome [7]. Dubois-Laforgue et al reported in one of the largest cohort studies on more than 200 adults a prevalence of 58% of hypertension in patients with RCAD syndrome.…”

Section: Discussionmentioning

confidence: 99%

Low prevalence of hypertension in children with renal cysts and diabetes syndrome is the hallmark of the disease

Seeman

Weigel

Bláhová

et al. 2021

Preprint

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Cystic kidney diseases such as autosomal recessive or dominant polycystic kidney disease (ARPKD and ADPKD) are associated with high prevalence of arterial hypertension. On the contrary, studies on hypertension in children with renal cysts and diabetes (RCAD) syndrome caused by abnormalities in the HNF1B gene are rare. Therefore, the aim of our study was to investigate the prevalence of hypertension in children with RCAD syndrome due to HNF1B gene abnormalities and to search for possible risk factors for development of hypertension. Data on all children with genetically proven RCAD syndrome from three pediatric nephrology tertiary centers were retrospectively reviewed (office blood pressure (BP), ambulatory blood pressure monitoring (ABPM), creatinine clearance, renal ultrasound, echocardiography, albuminuria/proteinuria). Hypertension was defined using the current ESH 2016 criteria and/or by the use of antihypertensive drugs. Thirty-two children with RCAD syndrome were investigated. Three children received ACE-inhibitors for hypertension and/or proteinuria. Hypertension was diagnosed using office BP in 22% of the children (n = 7) In the 7 performed ABPM 1 child (14%) was diagnosed with hypertension. Creatinine clearance, proteinuria, albuminuria, body mass index, enlargement or hypodysplasia of the kidneys and prevalence of HNF1B-gene deletion or mutation were not significantly different between hypertensive and normotensive children. Conclusion: Hypertension is rare in children with RCAD syndrome. The low prevalence of hypertension seems to be the hallmark of the disease.

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“…[1][2][3]5 HNF1B molecular defects are investigated especially in cases that present with renal cysts and diabetes. 2-4,8,12,13 Dotto et al 13 detected heterozygous HNF1B whole-gene deletion in one of 28 patients with renal cysts and prediabetes/diabetes, body and tail pancreatic agenesis and HNF1B mutation Inadequate insulin secretion of pancreatic beta cells is responsible for the diabetes in these patients. But, in some patients pancreatic atrophy, hypoplasia of pancreatic trunk, tail and neck were observed.…”

Section: Discussionmentioning

confidence: 99%

“…But, in some patients pancreatic atrophy, hypoplasia of pancreatic trunk, tail and neck were observed. [1][2][3][4][5]13,14 Hepatic insulin resistance was also shown in these patients. 15 Pancreatic imaging was not performed in our patient, whose diabetes etiology was considered to be MODY.…”

Section: Discussionmentioning

confidence: 99%

A case of familial recurrent 17q12 microdeletion syndrome presenting with severe diabetic ketoacidosis

Aydın¹,

Kıral²,

Susam³

et al. 2022

Turk J Pediatr

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Background. Heterozygous intragenic mutations of the hepatocyte nuclear factor 1 homeobox b gene (HNF1B) located on chromosome 17 and microdeletion of 17q12 region (17q12MD) leads to the complete loss of this gene, which causes renal cystic disease, diabetes mellitus (MODY5), hypomagnesemia, hyperuricemia, liver enzyme abnormalities, genital tract abnormalities and exocrine pancreatic insufficiency. In addition, patients with 17q12MD also have facial dysmorphism, neuro-developmental and neuropsychiatric disorders. Case. A 16-year-old girl with obesity and mild facial dysmorphism was admitted to the hospital with symptoms of diabetes that started two days prior to her admission. She was diagnosed with severe diabetic ketoacidosis and treated accordingly. She had been followed up with the diagnoses of multicystic renal disease, hydronephrosis, hepatosteatosis, hypomagnesemia and hyperuricemia since the age of six. She had mild intellectual disability. Her menarche started two months ago. Cranial magnetic resonance imaging revealed mild diffuse cerebral and cerebellar atrophy and a partial empty sella. Her mother had diabetes, hypomagnesemia and mild intellectual disability and her maternal grandfather and uncle had diabetes. Her grandfather also had renal cystic disease. All of them are on oral antidiabetic medication. The genetic analysis of the patient and her mother revealed a loss of 1.6 megabases in chromosome 17q12. Conclusions. MODY5 should be kept in mind in patients with diabetes who present with extra pancreatic findings, especially with renal cystic disease, more over, a genetic analysis including the study of 17q12MD should be carried out in patients who present with additional neuropsychiatric findings. Ketoacidosis can be seen in patients with MODY5. Ketoacidosis and renal anomalies and dysfunction are factors that increase and affect the severity of each other in these patients.

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Searching for mutations in the HNF1B gene in a Brazilian cohort with renal cysts and hyperglycemia

Cited by 7 publications

References 30 publications

Update on clinical screening of maturity-onset diabetes of the young (MODY)

Update on clinical screening of maturity-onset diabetes of the young (MODY)

Low prevalence of hypertension in children with renal cysts and diabetes syndrome is the hallmark of the disease

A case of familial recurrent 17q12 microdeletion syndrome presenting with severe diabetic ketoacidosis

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