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

Renata P Dotto,Milena Gurgel Teles,Luciana F Franco,André F Reis,Magnus R Dias-Da-Silva,Regina Célia M S Moisés,Fernando M A Giuffrida,José Luiz Nishiura,Susan C Lindsey,Ita P Heilberg,João R Sa,Lilian Araújo Caetano,Lucas Santos De Santana

doi:10.20945/2359-3997000000138

Renata P Dotto, Milena Gurgel Teles + Show 11 more

Open Access

https://doi.org/10.20945/2359-3997000000138

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Abstract

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. 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. 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. 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).

Highlights

M aturity-onset diabetes of the young (MODY) is characterized by the occurrence of earlyonset diabetes mellitus (DM), most often before age 25, with dominant autosomal inheritance caused by primary defects in insulin secretion
The objective of our study was to verify the presence of variants in the HNF1B gene in a sample of the Brazilian population selected according to the presence of renal cysts and hyperglycemia
92 7 a DM and prediabetes according to ADA criteria; b HbA1c measured by HPLC

Summary

Introduction

M aturity-onset diabetes of the young (MODY) is characterized by the occurrence of earlyonset diabetes mellitus (DM), most often before age 25, with dominant autosomal inheritance caused by primary defects in insulin secretion. The HNF1B gene was associated with cystic kidney disease shortly after being first described as a cause of MODY by Horikawa and cols. It is noteworthy that not all patients carrying an HNF1B mutation have renal cysts or DM [5].

Results

Conclusion