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A loss-of-function AGTR1 variant in a critically-ill infant with renal tubular dysgenesis: case presentation and literature review

journal contribution
submitted on 2024-07-28, 08:08 and posted on 2024-07-28, 10:34 authored by Aljazi Al-Maraghi, Waleed Aamer, Mubarak Ziab, Elbay Aliyev, Najwa Elbashir, Sura Hussein, Sasirekha Palaniswamy, Dhullipala Anand, Donald R. Love, Adrian Charles, Ammira A.S.Akil, Khalid A. Fakhro

Background

Renal tubular dysgenesis (RTD) is a severe disorder with poor prognosis significantly impacting the proximal tubules of the kidney while maintaining an anatomically normal gross structure. The genetic origin of RTD, involving variants in the ACE, REN, AGT, and AGTR1 genes, affects various enzymes or receptors within the Renin angiotensin system (RAS). This condition manifests prenatally with oligohydramninos and postnatally with persistent anuria, severe refractory hypotension, and defects in skull ossification.

Case presentation

In this report, we describe a case of a female patient who, despite receiving multi vasopressor treatment, experienced persistent hypotension, ultimately resulting in early death at five days of age. While there was a history of parental consanguinity, no reported family history of renal disease existed. Blood samples from the parents and the remaining DNA sample of the patient underwent Whole Genome Sequencing (WGS). The genetic analysis revealed a rare homozygous loss of function variant (NM_000685.5; c.415C > T; p.Arg139*) in the Angiotensin II Receptor Type 1 (AGTR1) gene.

Conclusion

This case highlights the consequence of loss-of-function variants in AGTR1 gene leading to RTD, which is characterized by high mortality rate at birth or during the neonatal period. Furthermore, we provide a comprehensive review of previously reported variants in the AGTR1 gene, which is the least encountered genetic cause of RTD, along with their associated clinical features.

Other Information

Published in: BMC Nephrology
License: https://creativecommons.org/licenses/by/4.0
See article on publisher's website: https://dx.doi.org/10.1186/s12882-024-03569-z

Funding

Qatar National Research Fund (NPRP11S-0110–180250), The PMED-Qatar Study: Personalized Molecular Evaluation and Diagnosis for Rare Diseases in Qatar.

History

Language

  • English

Publisher

Springer Nature

Publication Year

  • 2024

License statement

This Item is licensed under the Creative Commons Attribution 4.0 International License.

Institution affiliated with

  • Hamad Bin Khalifa University
  • College of Health and Life Sciences - HBKU
  • Sidra Medicine
  • Clinical Research Centre - Sidra Medicine
  • Weill Cornell Medicine - Qatar

Geographic coverage

Middle East

Related Datasets

Al-Maraghi, Aljazi; Aamer, Waleed; Ziab, Mubarak; Aliyev, Elbay; Elbashir, Najwa; Hussein, Sura; et al. (2024). A loss-of-function AGTR1 variant in a critically-ill infant with renal tubular dysgenesis: case presentation and literature review. Accession number VCV002430252.2. Last modified 2023. National Library of Medicine : National Center for Biotechnology Information : ClinVar. https://www.ncbi.nlm.nih.gov/clinvar/variation/2430252/

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