Nature and recurrence of AVPR2 mutations in X-linked nephrogenic diabetes insipidus
- Universite de Montreal (Canada)
- McGill Univ., Montreal (Canada)
- Baylor College of Medicine, Houston, TX (United States)
- and others
X-linked nephrogenic diabetes insipidus (NDI) is a rare disease with defective renal and extrarenal arginine-vasopressin V[sub 2] receptor responses due to mutations in the AVPR2 gene in Xq28. The authors 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, 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. 25 refs., 2 figs., 2 tabs.
- OSTI ID:
- 6872387
- Journal Information:
- American Journal of Human Genetics; (United States), Vol. 55:2; ISSN 0002-9297
- Country of Publication:
- United States
- Language:
- English
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KIDNEYS
HEREDITARY DISEASES
RECEPTORS
GENE MUTATIONS
WATER
HOMEOSTASIS
HUMAN X CHROMOSOME
BODY
CHROMOSOMES
DISEASES
HETEROCHROMOSOMES
HUMAN CHROMOSOMES
HYDROGEN COMPOUNDS
MEMBRANE PROTEINS
MUTATIONS
ORGANIC COMPOUNDS
ORGANS
OXYGEN COMPOUNDS
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550400* - Genetics