Novel AVPR2 mutations and clinical characteristics in 28 Chinese families with congenital nephrogenic diabetes insipidus.
Adolescent
Age of Onset
China
/ epidemiology
Cognitive Dysfunction
/ epidemiology
Diabetes Insipidus, Nephrogenic
/ diagnosis
Diagnostic Techniques, Urological
Dwarfism
/ diagnosis
Genetic Association Studies
Humans
Mutation
Osmolar Concentration
Pedigree
Receptors, Vasopressin
/ genetics
Ultrasonography
/ methods
Urinalysis
/ methods
Urologic Diseases
/ congenital
Aquaporin 2
Mutation
Nephrogenic diabetes insipidus
Vasopressin V2 receptor
Water resorption
Journal
Journal of endocrinological investigation
ISSN: 1720-8386
Titre abrégé: J Endocrinol Invest
Pays: Italy
ID NLM: 7806594
Informations de publication
Date de publication:
Dec 2021
Dec 2021
Historique:
received:
21
04
2021
accepted:
02
06
2021
pubmed:
9
6
2021
medline:
19
2
2022
entrez:
8
6
2021
Statut:
ppublish
Résumé
To investigate genotype and phenotype of congenital nephrogenic diabetes insipidus caused by AVPR2 mutations, which is rare and limitedly studied in Chinese population. 88 subjects from 28 families with NDI in a department (Beijing, PUMCH) were screened for AVPR2 mutations. Medical records were retrospectively reviewed and characterized. Genotype and phenotype analysis was performed. 23 AVPR2 mutations were identified, including six novel mutations (p.Y117D, p.W208R, p.L313R, p.S127del, p.V162Sfs*30 and p.G251Pfs*96). The onset-age ranged from 1 week to 3 years. Common presentations were polydipsia and polyuria (100%) and intermittent fever (57%). 21% and 14% of patients had short stature and mental impairment. Urine SG and osmolality were decreased, while serum osmolality and sodium were high. Urological ultrasonography results showed hydronephrosis of the kidney (52%), dilation of the ureter (48%), and thickened bladder wall or increased residual urine (32%), led to intermittent urethral catheterization (7%), cystostomy (11%) and binary nephrostomy (4%). Urological defects were developed in older patients. Genotype and phenotype analysis revealed patients with non-missense mutations had higher levels of serum sodium than missense mutations. In the first and largest case series of NDI caused by AVPR2 mutations in Chinese population, we established genetic profile and characterized clinical data, reporting six novel mutations. Further, we found genotype was associated with phenotype. This knowledge broadens genotype and phenotype spectrum of rare congenital NDI caused by AVPR2 mutations, and provides basis for studying molecular biology of AVPR2.
Identifiants
pubmed: 34101133
doi: 10.1007/s40618-021-01607-3
pii: 10.1007/s40618-021-01607-3
doi:
Substances chimiques
AVPR2 protein, human
0
Receptors, Vasopressin
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2777-2783Subventions
Organisme : National Natural Science Fund
ID : 81670814
Organisme : National Natural Science Fund
ID : 81970757
Organisme : National Key R&D Program of China
ID : 2018YFA 0800801
Informations de copyright
© 2021. Italian Society of Endocrinology (SIE).
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