Two novel mutations in the coding region for neurophysin-II associated with familial central diabetes insipidus

Journal Article · Sat Apr 01 04:00:00 EST 1995 · Journal of Clinical Endocrinology and Metabolism

DOI:https://doi.org/10.1210/jc.80.4.1352· OSTI ID:219854

Nagasaki, Hiroshi; Ito, Masafumi; Yuasa, Hiromitsu ^[1]

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1. Nagoya Univ. School of Medicine (Japan); and others

Familial central diabetes insipidus is an autosomal dominant disease caused by a deficiency of arginine vasopressin (AVP). We previously reported three distinct mutations in the AVP gene in Japanese familial central diabetes insipidus pedigrees that result in substitution of Ser for Gly{sup 57} in the neurophysin-II (NPII) moiety of the AVP precursor, a substitution of Thr for Ala at the COOH-terminus of the signal peptide, and a deletion of Glu{sup 47} in the NPII moiety. In this study, we analyzed the AVP gene in two pedigrees by direct sequencing of the polymerase chain reaction-amplified DNA and found two novel mutations in exon 2, which encodes the central part of the NPII moiety of the precursor. The mutation in one pedigree was a C to A transition at nucleotide position 1891, which replaces Cys{sup 67} (TGC) with stop codon (TGA). As the premature termination eliminates part of the COOH domain of the NPII moiety and the glycoprotein moiety, the conformation of the truncated protein is likely to be markedly different from that of normal precursor. In another pedigree, a G to T transversion was detected at nucleotide position 1874, which substitutes polar Trp (TGG) for hydrophobic Gly{sup 62}(GGG). It is possible that mutated NPII molecules, as a consequence of a conformational change, cannot bind AVP or self-associate to form higher oligomer complexes. Interestingly, all mutations we have identified to date, with the exception of the signal peptide mutation, are located in exon 2, suggesting the importance of the highly conserved central part of the NPII molecules and/or the NPII moiety in the precursor for AVP synthesis. 21 refs., 5 figs., 2 tabs.

• OSTI ID: 219854
• Journal Information: Journal of Clinical Endocrinology and Metabolism, Journal Name: Journal of Clinical Endocrinology and Metabolism Journal Issue: 4 Vol. 80; ISSN JCEMAZ; ISSN 0021-972X
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
AMINO ACIDS
ARGININE
BIOSYNTHESIS
CODONS
DNA SEQUENCING
DOMINANT MUTATIONS
ENDOCRINE DISEASES
EXONS
GENE MUTATIONS
GENES
GENETICS
HEREDITARY DISEASES
JAPAN
METABOLIC DISEASES
NUCLEOTIDES
PATIENTS
POLYMERASE CHAIN REACTION
VASOPRESSIN