Identificatie van een nieuwe mutatie (Cys116Gly) bij een familie met neurogene diabetes insipidus

Elucidation and identification of the molecular biological alteration in the arginine-vasopressin neurophysin II AVP-NPII gene in a family with familial neurohypophysial diabetes insipidus (FNDI).

Design

Descriptive.

Methods

Following the finding of diabetes insipidus in a 2-year-old boy and his father a molecular genetic investigation was performed in the Isala Klinieken, Sophia location, in Zwolle, the Netherlands, to determine the nature of a possible gene mutation. Thereafter the AVP-NPII gene was screened in the family with polymerase chain reaction (PCR) and restriction enzyme analysis on DNA isolated from peripheral blood. An extensive pedigree was made.

Results

A new mutation in the AVP-NPII gene was identified in the part encoding the transport peptide neurophysin II, in exon 3, on codon 116, in which thymine was replaced by guanine, leading to the amino acid glycine instead of cysteine in the gene product.

Conclusion

In a Dutch family with familial neurohypophysial diabetes insipidus a new gene mutation was found (Cys116Gly). Clarification of the molecular background of FNDI in this family made it possible to test family members in a relatively simple and friendly way (without the thirsting test) by PCR and restriction enzyme analysis for the presence of the mutation and the predisposition for diabetes insipidus.