Search Results

You are looking at 1 - 2 of 2 items for

  • Author: Federico Baronio x
  • All content x
Clear All Modify Search
Free access

Antonio Balsamo, Alessandro Cicognani, Monia Gennari, Wolfgang G Sippell, Soara Menabò, Federico Baronio, and Felix G Riepe

Objective: The renal form of pseudohypoaldosteronism type 1 (PHA1) is a rare disease caused by mutations in the human mineralocorticoid receptor gene (NR3C2).

Design: Aim of the study was to analyze the NR3C2 gene in three Italian patients with clinical signs of renal PHA1 and to evaluate the distribution of the -2G > C, c.538A > G, and c.722C > T single nucleotide polymorphism (SNP) pattern in the PHA1 patients and in 90 controls of the same ethnic origin.

Methods: Analysis of the NR3C2 gene sequence and of the polymorphic SNP markers. Functional characterization of the detected novel NR3C2 mutations utilizing aldosterone-binding assays and reporter gene transactivation assays.

Results: One novel nonsense (Y134X) and one novel frameshift (2125delA) mutation were detected. They exhibited no aldosterone binding and no transactivation abilities. No mutation was detected in the third patient. Haploinsufficiency of NR3C2 was ruled out by microsatellite analysis in this patient. The c.722T SNP was detected in 97% of alleles in the Italian population which is significantly different from the general German or US population.

Conclusions: Molecular analysis of the NR3C2 gene in PHA1 patients is warranted to detect novel mutations in order to clarify the underlying genetic cause, which may extend the insight into relevant functional regions of the hMR protein. The effect the different distribution of the c.722T SNP is not clear to date. Further studies are necessary to provide evidence as to a possible advantage of a less sensitive hMR in southern countries.

Restricted access

Angela K Lucas-Herald, Jillian Bryce, Andreas Kyriakou, Marie Lindhardt Ljubicic, Wiebke Arlt, Laura Audí, Antonio Balsamo, Federico Baronio, Silvano Bertelloni, Markus Bettendorf, Antonia Brooke, Hedi L Claahsen-van der Grinten, Justin Davies, Gloria Hermann, Liat de Vries, Ieuan A Hughes, Rieko Tadokoro-Cuccaro, Feyza Darendeliler, Sukran Poyrazoglu, Mona Ellaithi, Olcay Evliyaoglu, Simona Fica, Lavinia Stejereanu, Aneta Gawlik, Evgenia Globa, Nataliya Zelinska, Tulay Guran, Ayla Güven, Sabine Hannema, Olaf Hiort, P-m Holterhus, Violeta Iotova, Vilhelm Mladenov, Vandana Jain, Rajni Sharma, Farida Jennane, Colin Johnston, Gil Guerra-Junior, Daniel Konrad, Odile Gaisl, Nils P Krone, Ruth Krone, Katherine Lachlan, Dejun Li, Corina Lichiardopol, Lidka Lisá, Renata Levoni Markosyan, Inas Mazen, Klaus Mohnike, Marek Niedziela, Anna Nordenstrom, Rodolfo A Rey, Mars Skae, Lloyd JW Tack, Jeremy W Tomlinson, Naomi Weintrob, Martine Cools, and S Faisal Ahmed

Objectives: To determine trends in clinical practice for individuals with DSD requiring gonadectomy.

Design: Retrospective cohort study.

Methods: Information regarding age at gonadectomy according to diagnosis; reported sex; time of presentation to specialist center; and location of center from cases reported to the International DSD Registry and who were over 16 years old in January 2019.

Results: Data regarding gonadectomy were available in 668 (88%) individuals from 44 centers. Of these, 248 (37%) (median age (range) 24 (17, 75) years) were male and 420 (63%) (median age (range) 26 (16, 86) years) were female. Gonadectomy was reported from 36 centers in 351/668 cases (53%). Females were more likely to undergo gonadectomy (n=311, p<0.0001). The indication for gonadectomy was reported in 268 (76%). The most common indication was mitigation of tumour risk in 172 (64%). Variations in the practice of gonadectomy were observed; of the 351 cases from 36 centers, 17 (5%) at 9 centers had undergone gonadectomy before their first presentation to the specialist center. Median age at gonadectomy of cases from high income countries and low/middle income countries (LMIC) was 13.0 yrs (0.1, 68) years and 16.5 yrs (1, 28), respectively (p<0.0001) with the likelihood of long-term retention of gonads being higher in LMIC countries.

Conclusions: The likelihood of gonadectomy depends on the underlying diagnosis, sex of rearing and the geographical setting. Clinical benchmarks, which can be studied across all forms of DSD will allow a better understanding of the variation in the practice of gonadectomy.