Nature and recurrence of AVPR2 mutations in X-linked nephrogenic diabetes insipidus

Journal Article · Mon Aug 01 04:00:00 EDT 1994 · American Journal of Human Genetics; (United States)

OSTI ID:6872387

Bichet, D G; Lonergan, M; Arthus, M F ^[1]; Goodyer, P ^[2]; Birnbaumer, M; Rosenthal, W ^[3]; Nivet, H; Benoit, S; Giampietro, P; Simonetti, S ^[4]

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1. Universite de Montreal (Canada)
2. McGill Univ., Montreal (Canada)
3. Baylor College of Medicine, Houston, TX (United States)
4. 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), Journal Name: American Journal of Human Genetics; (United States) Vol. 55:2; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

550400* -- Genetics
59 BASIC BIOLOGICAL SCIENCES
BODY
CHROMOSOMES
DISEASES
GENE MUTATIONS
HEREDITARY DISEASES
HETEROCHROMOSOMES
HOMEOSTASIS
HUMAN CHROMOSOMES
HUMAN X CHROMOSOME
HYDROGEN COMPOUNDS
KIDNEYS
MEMBRANE PROTEINS
MUTATIONS
ORGANIC COMPOUNDS
ORGANS
OXYGEN COMPOUNDS
PROTEINS
RECEPTORS
WATER
X CHROMOSOME