A new mutation of the arginine vasopressin-neurophysin II gene in a family with autosomal dominant neurohypophyseal diabetes insipidus.
Familial neurohypophyseal diabetes insipidus (FNDI) is an autosomally dominant inherited disorder with a typical onset at one to six years of age. The genetic locus of FNDI is the arginine vasopressin-neurophysin II (AVP-NPII) gene. The gene encoding the precursor hormone (prepro-AVP-neurophysin II) is located in the chromosomal region 20p13 and contains three exons. Mutations that cause FNDI have been found to occur within the signal peptide of the prepro-AVP-neurophysin II precursor, within the coding sequence for neurophysin II and the vasopressin-coding sequence. A family (four members with FNDI, two without FNDI) in three consecutive generations was investigated. Index case was a now 22-year old man with a history of severe polyuria (18 L/day) and polydipsia first recognized at about 4-5 months of age. The arginine vasopressin-neurophysin II gene was investigated by direct sequencing of PCR products amplified from each exon. Subsequently, a restriction analysis was performed to verify the sequencing results. The affected individuals were found to have a missense mutation in exon 2 at nucleotide position 1887 (G to C) of the AVP-NPII gene. Using both restriction enzyme digestion and sequence analysis, the mutation was found in all affected family members, but not in the unaffected members studied. This mutation (1887 G to C) represents a novel mutation of the AVP-NPII gene.
Mundschenk
J
J
Department of Endocrinology and Metabolism, University of Magdeburg, Germany.
Rittig
S
S
Siggaard
C
C
Hensen
J
J
Lehnert
H
H
D000328:Adult; D001120:Arginine; D001127:Arginine Vasopressin / Q000235:genetics*; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D003919:Diabetes Insipidus / Q000235:genetics*; D005091:Exons; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D009481:Neurophysins / Q000235:genetics*; D010375:Pedigree; D011392:Proline; D017422:Sequence Analysis, DNA
D009481:Neurophysins; D001127:Arginine Vasopressin; D001120:Arginine; D011392:Proline; D015252:Deoxyribonucleases, Type II Site-Specific; C038485:GGGCCC-specific type II deoxyribonucleases