Comment on Dubois-Laforgue et al. Diabetes, Associated Clinical Spectrum, Long-term Prognosis, and Genotype/Phenotype Correlations in 201 Adult Patients With Hepatocyte Nuclear Factor 1B (<i>HNF1B</i>) Molecular Defects. Diabetes Care 2017;40:1436–1443

Clissold, Rhian L; Ellard, Sian; Bingham, Coralie; Hattersley, Andrew T.

doi:10.2337/dc17-1672

Cited by 5 publications

(7 citation statements)

References 5 publications

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“…Similar results were found in other two previous studies (8,27). Some hypotheses could be raised based on these observations, as other genes affected by whole HNF1B gene deletions could also have a role in the clinical differences (17,28,29).…”

Section: Discussionsupporting

confidence: 90%

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

Dotto¹,

Santana²,

Lindsey³

et al. 2019

Archives of Endocrinology and Metabolism

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Objective To verify the presence of variants in HNF1B in a sample of the Brazilian population selected according to the presence of renal cysts associated with hyperglycemia. Subjects and methods We evaluated 28 unrelated patients with clinical suspicion of HNF1B mutation because of the concomitant presence of diabetes mellitus (DM) or prediabetes and renal cysts. Genotyping was accomplished using Sanger sequencing or multiplex ligation-dependent probe amplification (MLPA). In positive cases, available relatives were recruited. Results We found two patients with HNF1B mutations. The first presented the variant p.Pro328Leufs*48(c.983delC) and had DM, renal cysts, and hypomagnesemia. The second presented a heterozygous whole gene deletion in HNF1B, DM, renal cysts, body and tail pancreatic agenesis, and hypomagnesemia; this alteration was also found in his two siblings and his father. Conclusion The recruitment of suspected cases of HNF1B gene mutations in Brazilians due to hyperglycemia and renal cysts presents two positive cases. Our cases contribute to the annotation of clinical and biochemical phenotypes of this rare form of maturity-onset diabetes of the young (MODY).

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Section: Discussionsupporting

confidence: 90%

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

Dotto¹,

Santana²,

Lindsey³

et al. 2019

Archives of Endocrinology and Metabolism

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show abstract

“…One could have expected gene deletions and loss-of-function mutations with higher frequency in patients with more severe disease as has been reported for other kidney disorders [25,26]. However, this issue is controversially discussed, and other authors even describe a more favorable renal outcome in patients with gene deletions compared to other mutations in HNF1B [27][28][29]. Possible explanations include a dominant negative effect of HNF1B non-deletion mutations or the involvement of other genes located in the deletion interval on chromosome 17q12.3.…”

Section: Genotype-phenotype Correlationmentioning

confidence: 94%

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

et al. 2019

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Background HNF1B gene mutations are an important cause of bilateral (cystic) dysplasia in children, complicated by chronic renal insufficiency. The clinical variability, the absence of genotype-phenotype correlations, and limited long-term data render counseling of affected families difficult. Methods Longitudinal data of 62 children probands with genetically proven HNF1B nephropathy was obtained in a multicenter approach. Genetic family cascade screening was performed in 30/62 cases. Results Eighty-seven percent of patients had bilateral dysplasia, 74% visible bilateral, and 16% unilateral renal cysts at the end of observation. Cyst development was non-progressive in 72% with a mean glomerular filtration rate (GFR) loss of − 0.33 ml/min/ 1.73m 2 per year (± 8.9). In patients with an increase in cyst number, the annual GFR reduction was − 2.8 ml/min/1.73m 2 (± 13.2), in the total cohort − 1.0 ml/min/1.73m 2 (±10.3). A subset of HNF1B patients differs from this group and develops end stage renal disease (ESRD) at very early ages < 2 years. Hyperuricemia (37%) was a frequent finding at young age (median 1 year), whereas hypomagnesemia (24%), elevated liver enzymes (21%), and hyperglycemia (8%) showed an increased incidence in the teenaged Electronic supplementary material The online version of this article (

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“…We thank Clissold et al (1) for their comments on our article (2) that demonstrated genotype/phenotype correlations in patients with HNF1B molecular defects. We reported that, compared with the patients with an HNF1B mutation, those with HNF1B whole-gene deletion due to the 17q12 deletion were leaner at diagnosis and might have a more severe diabetes phenotype.…”

mentioning

confidence: 99%

“…They also had a better renal prognosis as suggested by a higher estimated glomerular filtration rate (eGFR) at diabetes diagnosis and at follow-up, a less frequent need for renal replacement by dialysis or renal transplantation, and a more frequent normal function at follow-up (49% vs. 22%) (2). Clissold et al (1) mentioned that previous studies showed similar results as regards renal function (3,4). Actually, in our article published in 2005 (5), which demonstrated that many patients with maturity-onset diabetes of the young 5 (MODY5) have an HNF1B deletion due to the 17q12 deletion, we already reported a higher eGFR in the 10 patients with the deletion compared with the 18 with a mutation (61 6 31.6 vs. 40 6 20.1 mL/min/1.73m 2 , respectively).…”

mentioning

confidence: 99%

“…However, probably owing to the small size of the studied population, the difference did not reach statistical significance (P 5 0.08). The two studies (3,4) quoted by Clissold et al (1) showed that patients with HNF1B deletion had a higher eGFR than those with truncating mutations. In two of these three previous studies, the patients with HNF1B mutations were significantly older than those with an HNF1B deletion at the time of eGFR estimates.…”

mentioning

confidence: 99%

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Response to Comment on Dubois-Laforgue et al. Diabetes, Associated Clinical Spectrum, Long-term Prognosis, and Genotype/Phenotype Correlations in 201 Adult Patients With Hepatocyte Nuclear Factor 1B (HNF1B) Molecular Defects. Diabetes Care 2017;40:1436–1443

et al. 2017

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Comment on Dubois-Laforgue et al. Diabetes, Associated Clinical Spectrum, Long-term Prognosis, and Genotype/Phenotype Correlations in 201 Adult Patients With Hepatocyte Nuclear Factor 1B (HNF1B) Molecular Defects. Diabetes Care 2017;40:1436–1443

Cited by 5 publications

References 5 publications

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

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

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

Response to Comment on Dubois-Laforgue et al. Diabetes, Associated Clinical Spectrum, Long-term Prognosis, and Genotype/Phenotype Correlations in 201 Adult Patients With Hepatocyte Nuclear Factor 1B (HNF1B) Molecular Defects. Diabetes Care 2017;40:1436–1443

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