This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Grant, F. D. Articles by Majzoub, J. A. Search for Related Content PubMed PubMed Citation Articles by Grant, F. D. Articles by Majzoub, J. A. Pubmed/NCBI databases Gene GEO Profiles HomoloGene OMIM Protein UniGene Compound via MeSH Substance via MeSH Medline Plus Health Information Diabetes Insipidus Hazardous Substances DB VASOPRESSIN

Two Novel Mutations of the Vasopressin Gene Associated with Familial Diabetes Insipidus and Identification of an Asymptomatic Carrier Infant¹

Endocrinology-Hypertension Division, Brigham and Women’s Hospital (F.D.G., C.M.H.), Division of Endocrinology and the Mental Retardation Research Center, The Children’s Hospital (F.D.G., J.A.M.), Program in Medical Science, Boston University School of Medicine (A.A.), and the Departments of Medicine (F.D.G., J.A.M.) and Pediatrics (J.A.M), Harvard Medical School, Boston, Massachusetts 02115

Address all correspondence and requests for reprints to: Frederick D. Grant, M.D., Endocrinology-Hypertension Division, Brigham and Women’s Hospital, 221 Longwood Avenue, Boston, Massachusetts 02115. E-mail: grantf{at}a1.tch.harvard.edu

Familial diabetes insipidus (FDI) is a syndrome of central vasopressin deficiency that is inherited in an autosomal dominant manner and that typically becomes clinically apparent in the first decade of life. Two novel mutations of the vasopressin gene have been identified in two previously unstudied kindreds with FDI. In each kindred, the inheritance of the FDI phenotype was consistent with an autosomal dominant mode of inheritance. In each proband, the diagnosis of central diabetes insipidus had been confirmed previously with a water deprivation protocol. After extraction of genomic DNA from each individual, the three exons of the vasopressin gene were separately amplified by PCR and directly sequenced using an automated dye termination method. In the proband and two other carriers of one kindred, a heterozygous C to T mutation was identified at nucleotide 1857. This is predicted to produce a serine to phenylalanine substitution at residue 56 of the vasopressin-related neurophysin peptide encoded by the mutated allele. The mutation also abolished an MspI site in the vasopressin sequence, and analysis of genomic DNA from eight members of the kindred (five with FDI) confirmed segregation of the mutation with the FDI phenotype. Another member of the kindred, a 13-month-old infant, also has the heterozygous C to T mutation, but a formal water balance study showed no evidence of diabetes insipidus. In the proband of the other kindred, a heterozygous G to A mutation was identified at nucleotide 1873. This mutation would be predicted to cause a cysteine to tyrosine substitution at residue 61 of the neurophysin encoded by the mutated allele. This heterozygous mutation was confirmed by the presence of an RsaI restriction site in one vasopressin allele in two members of the kindred. Therefore, two novel heterozygous mutations of the vasopressin gene have been identified in FDI kindreds. In one kindred, an asymptomatic carrier infant was identified and will require continued observation to determine whether she will develop clinical diabetes insipidus. The presence of these two novel mutations in a region of the vasopressin gene where other FDI mutations have been reported suggests that the part of the neurophysin peptide encoded by these sequences may be critically important in the appropriate expression of vasopressin.

This article has been cited by other articles:

				C. P. Mahoney, E. Weinberger, C. Bryant, M. Ito, J. L. Jameson, and M. Ito Effects of Aging on Vasopressin Production in a Kindred with Autosomal Dominant Neurohypophyseal Diabetes Insipidus Due to the {Delta}E47 Neurophysin Mutation J. Clin. Endocrinol. Metab., February 1, 2002; 87(2): 870 - 876. [Abstract] [Full Text] [PDF]

				J. P. H. Burbach, S. M. Luckman, D. Murphy, and H. Gainer Gene Regulation in the Magnocellular Hypothalamo-Neurohypophysial System Physiol Rev, July 1, 2001; 81(3): 1197 - 1267. [Abstract] [Full Text] [PDF]

				A. P. Abbes, B. Bruggeman, E. L.T. van den Akker, M. R. de Groot, A. A.M. Franken, V. R. Drexhage, and H. Engel Identification of Two Distinct Mutations at the Same Nucleotide Position, Concomitantly with a Novel Polymorphism in the Vasopressin-Neurophysin II Gene (AVP-NP II) in Two Dutch Families with Familial Neurohypophyseal Diabetes Insipidus Clin. Chem., October 1, 2000; 46(10): 1699 - 1702. [Full Text] [PDF]

				C. Siggaard, S. Rittig, T. J. Corydon, P. H. Andreasen, T. G. Jensen, B. S. Andresen, G. L. Robertson, N. Gregersen, L. Bolund, and E. B. Pedersen Clinical and Molecular Evidence of Abnormal Processing and Trafficking of the Vasopressin Preprohormone in a Large Kindred with Familial Neurohypophyseal Diabetes Insipidus due to A Signal Peptide Mutation J. Clin. Endocrinol. Metab., August 1, 1999; 84(8): 2933 - 2941. [Abstract] [Full Text]

				M. Nijenhuis, R. Zalm, and J. P. H. Burbach Mutations in the Vasopressin Prohormone Involved in Diabetes Insipidus Impair Endoplasmic Reticulum Export but Not Sorting J. Biol. Chem., July 23, 1999; 274(30): 21200 - 21208. [Abstract] [Full Text] [PDF]