Ann Lab Med.  2024 May;44(3):303-305. 10.3343/alm.2023.0361.

The First Case of Congenital Nephrogenic Diabetes Insipidus Caused by AVPR2 Disruption Because of 4q25 Insertional Translocation

• Kim B
• Ahn YH
• Park JH
• Lim HS
• Chae SW
• Lee JS
• Kang HG
• Kim MJ
• Seong MW

• KMID: 2555710
• DOI: http://doi.org/10.3343/alm.2023.0361

Figure

• 

  Fig. 1 AVPR2 next-generation sequencing and breakpoint analysis results. (A) Pedigree showing a typical X-linked recessive inheritance pattern. (B) Next-generation sequencing results revealed a soft clipped region in intron 2 of AVPR2. (C) Based on the results of analysis of the chimeric reads, PCR was performed targeting the suspected breakpoint. A fragment with the expected amplicon size of 400 bp was identified in gel electrophoresis. Sanger sequencing confirmed that the upstream from chrX:153,170,697 and the downstream from chr4:109,062,641 were joined. Specifically, exons 1–2 of AVPR2 and exons 1–3 of LEF1 were joined in opposite transcriptional orientations. (D) In chromosomal microarray analysis, a 497-kb heterozygous duplication in the 4q25 region was observed and described as “arr[GRCh37] 4q25(109062645_109559599)×3” according to the International System for Human Cytogenetic Nomenclature. (E) Based on the combined results, we concluded that a 497-kb insertional translocation occurred in the center of AVPR2.

Reference

References

1. Bockenhauer D, Bichet DG. 2015; Pathophysiology, diagnosis and management of nephrogenic diabetes insipidus. Nat Rev Nephrol. 11:576–88. DOI: 10.1038/nrneph.2015.89. PMID: 26077742.

2. Knoers N, Lemmink H. Adam MP, Everman DB, editors. 1993. Hereditary Nephrogenic Diabetes Insipidus. GeneReviews. University of Washington;Seattle:

3. Dufour W, Alawbathani S, Jourdain AS, Asif M, Baujat G, Becker C, et al. 2022; Monoallelic and biallelic variants in LEF1 are associated with a new syndrome combining ectodermal dysplasia and limb malformations caused by altered WNT signaling. Genet Med. 24:1708–21. DOI: 10.1016/j.gim.2022.04.022. PMID: 35583550.

4. Lévy J, Capri Y, Rachid M, Dupont C, Vermeesch JR, Devriendt K, et al. 2020; LEF1 haploinsufficiency causes ectodermal dysplasia. Clin Genet. 97:595–600. DOI: 10.1111/cge.13714. PMID: 32022899.