Endocrine Abstracts

Neurohypophyseal diabetes insipidus (DI) is said to be caused by familial forms in about 5% of cases¹. Hereditary transmission is autosomal dominant in most families and is caused by a mutation in the arginine vasopressin (AVP) gene on chromosome 20p13, which encodes for a large precursor hormone.

A 19-years old otherwise healthy patient seeked endocrine care for an inadequately treated DI. He reported about an undoubtful disease history with about 10 l of diluted urine without therapy since his second year of life. His father and sister were affected as well. Adjustment of the patient’s therapy resulted in a well-treated DI.

After informed consent, a genetic analysis was performed on the patient and his sister by sequence analysis of the AVP gene.

A hitherto undescribed heterozygous mutation p.Cys110 Arg in codon 110, exon 3 of the AVP gene was found, both in the patient and his sister. Since a stop mutation causing DI in the same codon has been described before² and since the mutation results in a non-conservative amino acid substitution, we conclude that this mutation is the cause for DI in this family.

Our findings add a new mutation to a list of 66 mutations so far described for the AVP gene (Biological Database HGMD Professional). Interestingly, the disease manifests not immediately after birth but later during the first and second year of life. This is in contrast to mutations in two other genes involved in familial DI (namely the arginine vasopressin receptor 2 gene and the vasopressin-sensitive water channel gene). Recent studies hypothesized that the disease is caused by formation of inclusion bodies hampering cell function³ and that there is a genotype–phenotype correlation⁴. Therefore, new mutations can add important information to the elucidation of the mechanisms that are involved in DI.

1. Baylis PH et al. Arch Dis Child 1998 79 84–89.

2. Rittig S et al. Am J Hum Genet 1996 58 107–117.

3. Arima H et al. J Nuroendocrinol 2010 22 754–57.

4. Siggaard C et al. Clin Endocrinol 2005 63 207–16.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.