ESPE Abstracts (2023) 97 P1-544

ESPE2023 Poster Category 1 Pituitary, Neuroendocrinology and Puberty (73 abstracts)

Clinical and laboratory characteristics of arginine vasopressin resistance and high carrier frequency of a novel homozygous variant p.R113C in the AQP2 gene among Buryats

Nina Makretskaya 1 , Ulyana Nanzanova 2 , Irina Hamaganova 2 , Elena Eremina 3 , Alexandra Filatova 1 , Mikhail Skoblov 1 & Anatoly Tiulpakov 1

1Research Centre for Medical Genetics, Moscow, Russian Federation. 2Children's Republican Clinical Hospital, Ulan-Ude, Russian Federation. 3Perinatal Center of Republica, Ulan-Ude, Russian Federation

Background: Congenital nephrogenic diabetes insipidus (arginine vasopressin resistance) is a rare inherited disorder characterized by insensitivity of the kidney to the antidiuretic effect of vasopressin. About 90% cases nephrogenic diabetes insipidus is an X-linked recessive disorder caused by variants in the AVP V2 receptor gene (AVPR2). In the remaining cases (10%) the disease is autosomal recessive or dominant and, for these patients, variants in the aquaporin 2 gene (AQP2) have been reported.

Aims: Description of 12 cases of arginine vasopressin resistance caused by a novel homozygous variant p.R113C in AQP2 among the indigenous population of the Republic of Buryatia. Study of the carrier frequency of the p.R113C variant in AQP2 among Buryats.

Methods: AQP2 was analyzed by the Sanger sequencing using the Genetic Analyzer Model 3130 sequencer in 12 patients with the phenotype of arginine vasopressin resistance. Genotyping of the nucleotide variant chr12:49951167C>T (c.337C>T p.R113C) was performed by Real-time PCR. 300 healthy individuals of Buryats origin were included in the study. Allele frequencies, Fisher’s confidence intervals were calculated using the WinPepi v.11.65 software.

Results: 12 patients from 11 families with arginine vasopressin resistance (female, n=5, male, n=7) were included in the study. The ethnicity of the subjects was Buryats. The mean age of patients was 3.0 years [2.3; 4.5]. All patients suffered from polyuria and polydipsia from the first year of life. Urine SG was decreased in all patients (Me 1001 g/L [1001; 1002]), serum osmolality was increase in 7 patients (Me 301.5 mOsm/kg [293; 307]), sodium levels were maintained at a relatively high level 144 mmol/L [139; 146]. The diagnosis of CNDI was established based on the results of a water deprivation test (lack of response to desmopressin administration). A homozygous variant c.337C>T p.R113C in AQP2 was detected in all patients. Among 300 analyzed samples the variant c.337C>T was detected in 5 cases in heterozygous state. The allele frequency of the studied variant was 0.008 (n=5/600, 95% CI=0.0017-0.016). Accordingly, the frequency of heterozygous carrier was 0.0167 (n=5/300). The frequency of arginine vasopressin resistance caused by variant c.337C>T in AQP2 among Buryats was 1: 14400 or 6.9 per 100,000 (95%CI=1:3906–1:346021 or 0,3-26 per 100,000). The frequency of heterozygous carriers of c.337C>T variant is 1:61 subjects (95%CI=1:32–1:294).

Conclusions: The results demonstrate high frequency of arginine vasopressin resistance due to the homozygous mutation p.R113C in AQP2 among Buryats, which is most likely attributed to a founder effect.

Volume 97

61st Annual ESPE (ESPE 2023)

The Hague, Netherlands
21 Sep 2023 - 23 Sep 2023

European Society for Paediatric Endocrinology 

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