Familial neurohypophyseal diabetes insipidus associated with a signal peptide mutation

Journal Article · Wed Sep 01 04:00:00 EDT 1993 · Journal of Clinical Endocrinology and Metabolism; (United States)

DOI:https://doi.org/10.1210/jcem.77.3.8370682· OSTI ID:5030876

McLeod, J F; Gaskill, M B; Bradley, G S; Robertson, G L ^[1]; Kovacs, L ^[2]; Rittig, S ^[3]

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1. Northwestern Univ. Medical School, Chicago, IL (United States)
2. Comenius Univ. Medical School, Bratislava (Slovakia)
3. Univ. of Aarhus, Aarhus (Denmark)

The authors studied the pathophysiology, natural history, and genetic basis of familial neurohypophyseal diabetes insipidus (FNDI) in a caucasian kindred. Twelve members had polyuria and a deficiency of plasma vasopressin (AVP), which progressed in severity over time. Another had normal urine volumes and plasma AVP when first tested at age 3 yr, but developed severe FNDI a year later. For unknown reasons, one man had a normal urine volume despite severe AVP deficiency and a history of polyuria in the past. When the AVP-neurophysin-II gene was amplified and sequenced, exon 2/3 was normal, but 7 of 12 clones of exon 1 contained a base substitution (G[yields]A) predicting a substitution of threonine for alanine at the -1 position of the signal peptide. Restriction analysis found the mutation in all 14 affected members, but in none of the 41 controls of 19 adult members with normal urine volumes and plasma or urinary AVP (lod score = 5.7). The mutation was also found in 2 infants in whom AVP was normal when tested at 6 and 9 months of age. We hypothesize that a mutation in exon 1 of the AVP-neurophysin-II gene caused FNDI in this kindred by making an abnormally processed precursor that gradually destroys vasopressinergic neurons. 46 refs., 6 figs.

• OSTI ID: 5030876
• Journal Information: Journal of Clinical Endocrinology and Metabolism; (United States), Journal Name: Journal of Clinical Endocrinology and Metabolism; (United States) Vol. 77:3; ISSN JCEMAZ; ISSN 0021-972X
• Country of Publication: United States
• Language: English

Related Subjects

550400* -- Genetics
550900 -- Pathology
59 BASIC BIOLOGICAL SCIENCES
BIOSYNTHESIS
CLONING
DNA HYBRIDIZATION
DNA SEQUENCING
DNA-CLONING
GENE MUTATIONS
HORMONES
HYBRIDIZATION
MUTATIONS
ORGANIC COMPOUNDS
PEPTIDE HORMONES
PITUITARY HORMONES
PROTEINS
RFLPS
STRUCTURAL CHEMICAL ANALYSIS
SYNTHESIS
VASOPRESSIN