A Novel Form of Familial Vasopressin Deficient Diabetes Insipidus Transmitted in an X-linked Recessive Manner.

Autor:	Habiby R; Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA., Bichet DG; Renal Genetic Laboratory, Hôpital du Sacré-Coeur de Montreal, Department of Medicine, University of Montreal, Montreal, Quebec, Canada., Arthus MF; Renal Genetic Laboratory, Hôpital du Sacré-Coeur de Montreal, Department of Medicine, University of Montreal, Montreal, Quebec, Canada., Connaughton D; Department of Medicine, Boston Children's Hospital, Boston, Massachusetts, USA., Shril S; Department of Medicine, Boston Children's Hospital, Boston, Massachusetts, USA., Mane S; Department of Medicine, Yale University School of Medicine, New Haven, Connecticut, USA., Majmundar AJ; Department of Medicine, Boston Children's Hospital, Boston, Massachusetts, USA., Hildebrandt F; Department of Medicine, Boston Children's Hospital, Boston, Massachusetts, USA., Robertson GL; Department of Medicine (Emeritus), Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Jazyk:	angličtina
Zdroj:	The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2022 May 17; Vol. 107 (6), pp. e2513-e2522.
DOI:	10.1210/clinem/dgac076
Abstrakt:	Context: Familial pituitary diabetes insipidus has been described only in an autosomal dominant or recessive mode of inheritance. Objective: This work aims to determine the cause of a novel form of familial diabetes insipidus (DI) that is controlled by desmopressin therapy but segregates in an X-linked recessive manner. Methods: Thirteen members from 3 generations of the kindred with familial DI were studied. Water intake, urine volume, urine osmolality, plasma osmolality, and plasma vasopressin were measured under basal conditions, during fluid deprivation, 3% saline infusion, and water loading. Magnetic resonance images of the posterior pituitary also were obtained. In affected males, the effects of desmopressin therapy and linkage of the DI to markers for chromosome Xq28 were determined. In addition, the genes encoding vasopressin, aquaporin-2, the AVPR2 receptor, and its flanking regions were sequenced. Results: This study showed that 4 males from 3 generations of the kindred have DI that is due to a deficiency of vasopressin, is corrected by standard doses of desmopressin, and segregates with markers for the AVPR2 gene in Xq28. However, no mutations were found in AVPR2 or its highly conserved flanking regions. Exome sequencing confirmed these findings and also revealed no deleterious variants in the provasopressin and aquaporin-2 genes. The 4 obligate female carriers osmo-regulated vasopressin in the low normal range. Conclusion: X-linked recessive transmission of DI can be due to a defect in either the secretion or the action of vasopressin. Other criteria are necessary to differentiate and manage the 2 disorders correctly. (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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