Abstract
X-linked nephrogenic diabetes insipidus (NDI, OMIM#304800) is caused by mutations in the arginine vasopressin (AVP, OMIM*192340) receptor type 2 (AVPR2, OMIM*300538) gene. A 20-month-old boy and his 8-year-old brother presented with polyuria, polydipsia, and failure to thrive. Both boys demonstrated partial DDAVP (1-desamino-8-D AVP or desmopressin) responses; thus, NDI diagnosis was delayed. While routine sequencing of AVPR2 showed a potential splice site variant, it was not until exome sequencing confirmed the AVPR2 splice site variant and did not reveal any more likely candidates that the patients' diagnosis was made and proper treatment was instituted. Both patients were hemizygous for two AVPR2 variants predicted in silico to affect AVPR2 messenger RNA (mRNA) splicing. A minigene assay revealed that the novel AVPR2 c.276A>G mutation creates a novel splice acceptor site leading to 5' truncation of AVPR2 exon 2 in HEK293 human kidney cells. Both patients have been treated with high-dose DDAVP with a remarkable improvement of their symptoms and accelerated linear growth and weight gain. We present here a unique case of partial X-linked NDI due to an AVPR2 splice site mutation; patients with diabetes insipidus of unknown etiol...Continue Reading
References
Nov 30, 2000·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·K KamperisS Rittig
Feb 13, 2001·Molecular Genetics and Metabolism·K NakamuraN Kondo
Feb 17, 2001·American Journal of Human Genetics·S A SlaugenhauptJ F Gusella
Oct 19, 2007·Clinical Endocrinology·Mia FaerchSøren Rittig
Aug 30, 2008·Journal of Cellular Physiology·Elias SpanakisClaudia Gragnoli
Oct 29, 2009·Proceedings of the National Academy of Sciences of the United States of America·Murim ChoiRichard P Lifton
May 12, 2011·JAMA : the Journal of the American Medical Association·William A Gahl, Cynthia J Tifft
Jul 6, 2011·Nature Reviews. Endocrinology·Muriel BabeyGary L Robertson
Jan 13, 2012·Genetics in Medicine : Official Journal of the American College of Medical Genetics·William A GahlDavid Adams
Mar 6, 2012·Metabolism: Clinical and Experimental·Vassos NeocleousLeonidas A Phylactou
Mar 20, 2012·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Daniel WescheNine V A M Knoers
Nov 7, 2012·Nature·UNKNOWN 1000 Genomes Project ConsortiumGil A McVean
Jan 31, 2013·Endocrine Reviews·Hanne B MoellerRobert A Fenton
Mar 7, 2014·American Journal of Physiology. Renal Physiology·Kristian Vinter JuulJens Peter Nørgaard
Citations
Sep 10, 2020·Molecular Syndromology·Ji-Shi LiuLiang-Liang Fan
Mar 18, 2016·Clinical Kidney Journal·Daniel G BichetJasmin Levallois-Gignac
Apr 28, 2019·Medicine·Min ZhangDean Tian
Nov 22, 2020·Pharmacological Reviews·Torsten Schöneberg, Ines Liebscher