Novel de novo AVPR2 Variant in a Patient with Congenital Nephrogenic Diabetes Insipidus

Joshi, Shivani; Brandström, Per; Gregersen, Niels; Rittig, Søren; Christensen, Jane H.

doi:10.1159/000480009

Cited by 6 publications

(2 citation statements)

References 14 publications

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“…In our study, only 2 male family members (II-1 and III-3) presented with NDI phenotypes, the proband's mother (II-5) and his cousin (III-1) were heterozygous carriers and were asymptomatic. The novel AVPR2 mutation (c.547G>A; p.V183M) is located in the third extracellular domain, which is responsible for AVP recognition and binding [Joshi et al, 2017]. This mutation may disrupt the structure of the extracellular domain and reduce the recognition and binding of AVP, and finally break the water homeostasis and lead to NDI.…”

Section: Discussionmentioning

confidence: 99%

Identification of a Novel Arginine Vasopressin Receptor 2 Mutation (p.V183M) in a Chinese Family with Nephrogenic Diabetes Insipidus

et al. 2020

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Loss of function of arginine vasopressin receptor 2 (AVPR2) may affect the recognition and binding of arginine vasopressin (AVP) which, in turn, may prevent the activation of Gs/ adenylate cyclase and reduce the reabsorption of water by renal tubules and combined tubes. Finally, the organism may suffer from nephrogenic diabetes insipidus (NDI), a kind of kidney disorder featured by polyuria and polydipsia, due to a break of water homeostasis. In this study, we enrolled a Chinese family with polyuria and polydipsia. The proband presented abnormal fluid intake and excessive urine output. A water deprivation and AVP stimulation test further indicated that this patient had NDI. By sequencing known causative genes for diabetes insipidus, we identified a novel mutation in AVPR2 (c.547G>A; p.V183M) in the family. This mutation, located in a conserved site of AVPR2 and predicted to be disease-causing by informatics programs, was absent in our 200 controls and other public databases. Our study not only further confirms the clinical diagnosis, but also expands the spectrum of AVPR2 mutations and contributes to genetic diagnosis and counseling of patients with NDI.

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Section: Discussionmentioning

confidence: 99%

Identification of a Novel Arginine Vasopressin Receptor 2 Mutation (p.V183M) in a Chinese Family with Nephrogenic Diabetes Insipidus

et al. 2020

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“…Early clinical manifestations of CNDI in neonates are atypical and include recurrent irritability, vomiting, feeding difficulties, slow body weight gain, hyperpyrexia, constipation and dehydration[ 10 ]. A lack of understanding of the disease by clinicians causes frequent misdiagnoses or missed diagnoses, which may result in failure to administer treatments in time and ultimately leads to severe complications such as mental retardation, growth retardation, hydronephrosis, renal insufficiency or serious electrolyte disturbance, which can be fatal[ 11 , 12 ]. Therefore, in cases of neonates exhibiting pyrexia of unknown cause accompanied by hypernatremia that is difficult to correct, diabetes insipidus should be considered when no significant abnormalities are found regarding infection indicators and when antibiotic treatments are ineffective.…”

Section: Discussionmentioning

confidence: 99%

Congenital nephrogenic diabetes insipidus due to the mutation in AVPR2 (c.541C>T) in a neonate: A case report

Lin

et al. 2020

WJCC

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BACKGROUND Congenital nephrogenic diabetes insipidus (CNDI) is a rare hereditary renal disorder that is caused by mutations in AVPR2 or aquaporin 2 ( AQP2 ). Up to now, there are few reports about CNDI in neonates. Early clinical manifestations of CNDI in neonates are atypical. A lack of understanding of the disease by clinicians causes frequent misdiagnoses or missed diagnoses, which may result in failure to administer treatments in time and ultimately leads to severe complications. In this study, clinical data of a case of AVPR2 gene mutation-induced CNDI, which was confirmed by genetic testing, were retrospectively analyzed to improve our understanding of this disease. CASE SUMMARY On February 1, 2020, a male neonate was hospitalized 17 d after birth due to a 7 d period of pyrexia. The patient’s symptoms included recurrent pyrexia, hypernatremia and hyperchloremia, which were difficult to treat. The patient was fed on demand, and water was additionally provided between milk intakes. A combination treatment of hydrochlorothiazide and amiloride was administered. After the treatment, body temperature and electrolyte levels returned to normal, the volume of urine was significantly reduced and the patient was subsequently discharged. Genetic tests confirmed that the patient carried the AVPR2 gene missense mutation c.541C>T (P.R181C), and the patient’s mother carried a heterozygous mutation at the same locus. After clinical treatment with a combination of hydrochlorothiazide and amiloride, the body temperature and electrolyte levels returned to normal. Up until the most recent follow-up examination, normal body temperature, electrolyte levels and growth and development were observed. CONCLUSION CNDI in the neonatal period is rare, and its clinical manifestations are unspecific with some patients merely showing recurrent fever and electrolyte disturbance. Genetic testing of AVPR2 and AQP2 can be used for screening and genetic diagnosis of CNDI.

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Hereditary Neurohypophyseal Diabetes Insipidus

Rutishauser

Beuret

Prescianotto-Baschong

et al. 2019

Experientia Supplementum

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Neurohypophyseal diabetes insipidus (DI) is most often caused by trauma, including operations, and infiltrating processes in the hypothalamic-pituitary region. Irradiation, ischemia, infections, or autoimmunity can also underlie the disease. Since the middle of the 19 th century, familial forms of neurohypophyseal DI have been described. Most commonly, the disease is transmitted in an autosomal-dominant fashion; very rarely, autosomal-recessive inheritance has been observed. Hereditary neurohypophyseal DI is caused by mutations in the gene encoding the antidiuretic hormone vasopressin (AVP) and its carrier protein neurophysin II (NPII). Symptoms result from the lack of hormone, or from the inability of mutant AVP to activate its renal receptor, and respond to treatment with desmopressin (DDAVP). Dominant mutations cause retention of the hormone precursor in the endoplasmic reticulum (ER) of vasopressinergic neurons in the hypothalamus, resulting in cellular dysfunction and eventually neuronal death. This so-called "neurotoxicity hypothesis" was initially established on the basis of autopsy studies in affected humans and has been supported by heterologous cell-culture expression experiments and murine knock-in models. Current data show that retained mutants fail to be eliminated by the cell's quality control system and accumulate in fibrillar aggregations within the ER. Autosomal-dominant neurohypophyseal DI may thus be viewed as a neurodegenerative disease confined to vasopressinergic neurons.

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Novel de novo AVPR2 Variant in a Patient with Congenital Nephrogenic Diabetes Insipidus

Cited by 6 publications

References 14 publications

Identification of a Novel Arginine Vasopressin Receptor 2 Mutation (p.V183M) in a Chinese Family with Nephrogenic Diabetes Insipidus

Identification of a Novel Arginine Vasopressin Receptor 2 Mutation (p.V183M) in a Chinese Family with Nephrogenic Diabetes Insipidus

Congenital nephrogenic diabetes insipidus due to the mutation in AVPR2 (c.541C>T) in a neonate: A case report

Hereditary Neurohypophyseal Diabetes Insipidus

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