Nature and Recurrence of AVPR2 Mutations in X-Linked Nephrogenic Diabetes Insipidus
| Title: | Nature and Recurrence of AVPR2 Mutations in X-Linked Nephrogenic Diabetes Insipidus |
|---|---|
| Authors: | Bichet, Daniel G.; Birnbaumer, Mariel; Lonergan, Michele; Arthus, Marie-Francoise; Rosenthal, Walter; Goodyer, Paul; Nivet, Hubert; Benoit, Stephane; Giampietro, Philip; Simonetti, Simonetta; Kaplan, Bernard S.; Robertson, Gary; Hendy, PhD, Geoffrey N.; Fujiwara, T. Mary; Morgan, Kenneth |
| Publisher: | American Journal of Human Genetics |
| Date Published: | August 01, 1994 |
| Reference Number: | 94 |
X-linked nephrogenic diabetes insipidus (NDI) is a rare disease with defective renal and extrarenal arginine-vaso-pressin V2 receptor responses due to mutations in the AVPR2 gene in Xq28. We analyzed 31 independent NDI families to determine the nature and recurrence of AVPR2 mutations. Twenty-one new putative disease-causing mutations were identified: 113delCT, 253del35, 255del9, 274insG, V88M, R106C, 402delCT, C112R, Y124X, S126F, W164S, S167L, 684delTA, 804insG, W284X, A285P, W293X, R337X, and three large deletions or gene rearrangements. Five other mutations--R113W, Y128S, R137H, R181C, and R202C--that previously had been reported in other families were detected. There was evidence for recurrent mutation for four mutations (R113W, R137H, S167L, and R337X). Eight de novo mutation events were detected (274insG, R106C, Y128S, 167L [twice], R202C, 684delTA, and R337X). The origins were maternal (one), grandmaternal (one), and grandpaternal (six). In the 31 NDI families and 6 families previously reported by us, there is evidence both for mutation hot spots for nucleotide substitutions and for small deletions and insertions. More than half (58%) of the nucleotide substitutions in 26 families could be a consequence of 5-methyl-cytosine deamination at a CpG dinucleotide. Most of the small deletions and insertions could be attributed to slipped mispairing during DNA replication.
|
You may, however, read this article at the American Journal of Human Genetics website. To return to this page, use your "back" key. |
This translation by the NDI Foundation is to assist the lay reader. To provide a clear, accessible interpretation of the original article, we eliminated or simplified some technical detail and complicated scientific language. We concentrated our translation on those aspects of the article dealing directly with NDI. The NDI Foundation thanks the researchers for their work toward understanding and more effectively treating this disorder.
© Copyright NDI Foundation 2007 (JC)
Each gene is responsible for manufacturing a specific protein. Genes are segments of the hereditary substance (DNA) that comprises the chromosomes in the nuclei of cells. Each DNA strand is a string of four nucleotide bases: adenine, (A), cytosine (C), guanine (G), and thymine (T). These bases are combined in various orders. For example, a part of a gene's base sequence might look like this: GCCTCTAGTCGGCAG. Cells have a decoding apparatus that reads the base sequences three at a time (e.g. CAG). Each unit of three bases is called a codon. Each codon codes for a single amino acid (the building blocks of protein). There are many different types of mutations, and each can result in the gene producing a faulty protein.
In their study, Bichet, et al., found:
- Thirteen missense mutations -- a type of mutation that changes a codon so that it codes for a different amino acid than is required,
- Six nonsense mutations -- a mutation in which one of the three codons that ends the gene sequence appears in the middle of the gene sequence. This results in an incomplete and usually non-functional polypeptide,
- One in-frame deletion,
- Five deletion mutations (where bases are missing), and
- Five insertion mutations (where an extra base is inserted in the sequence).
The authors noted that a family may have no history of X-linked NDI in their lineage, yet still have a member who is born with NDI. This is because a new mutation that results in NDI could arise and be passed to a male offspring. But families with a history of NDI can take advantage of early, even prenatal, genetic analysis to provide timely and adequate treatment. X-linked NDI can manifest in the first days after birth. It is marked by extreme, excessive thirst and urination with an accompanying possibility of severe dehydration which could cause physical and mental retardation, and even death. Knowing that the newborn will have NDI can prepare the family and doctors to give immediate treatment and avoid the possible consequences of the disorder.