Kidney Week

Abstract: FR-PO654

Exome Sequencing Reveals a Monogenic Cause of Kidney Disease in 34% of Pediatric Patients at a Single Saudi Arabian Center

Session Information

• Genetic Kidney Diseases: Cohort Studies - Genetic Associations and Diagnoses
  October 25, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1202 Genetic Diseases of the Kidneys: Non-Cystic

Authors

• Lemberg, Katharina, Boston Children's Hospital, Boston, Massachusetts, United States

Katharina Lemberg, MD

• Shalaby, Mohamed Ahmed, King Abdulaziz University, Jeddah, Makkah, Saudi Arabia

Mohamed Ahmed Shalaby, MD, MBBS, MS

• Shril, Shirlee, Boston Children's Hospital, Boston, Massachusetts, United States

Shirlee Shril

• Buerger, Florian, Boston Children's Hospital, Boston, Massachusetts, United States

Florian Buerger, MD, PhD

• Schneider, Ronen, Boston Children's Hospital, Boston, Massachusetts, United States

Ronen Schneider, MD

• Yousef, Kirollos, Boston Children's Hospital, Boston, Massachusetts, United States

Kirollos Yousef, MBChB, MS

• Mertens, Nils David, Boston Children's Hospital, Boston, Massachusetts, United States

Nils David Mertens, MD

• Mansour, Bshara, Boston Children's Hospital, Boston, Massachusetts, United States

Bshara Mansour, MD

• Kolvenbach, Caroline Maria, Boston Children's Hospital, Boston, Massachusetts, United States

Caroline Maria Kolvenbach, MD, DrMed

• Merz, Lea Maria, Boston Children's Hospital, Boston, Massachusetts, United States

Lea Maria Merz, DrMed, ScM

• Saida, Ken, Boston Children's Hospital, Boston, Massachusetts, United States

Ken Saida, MD, PhD

• Deutsch, Konstantin, Boston Children's Hospital, Boston, Massachusetts, United States

Konstantin Deutsch, MD

• Hölzel, Selina, Boston Children's Hospital, Boston, Massachusetts, United States

Selina Hölzel

• Yu, Seyoung, Boston Children's Hospital, Boston, Massachusetts, United States

Seyoung Yu, MS

• Elmubarak, Izzeldin, Boston Children's Hospital, Boston, Massachusetts, United States

Izzeldin Elmubarak, MD

• Braun, Alina, Boston Children's Hospital, Boston, Massachusetts, United States

Alina Braun, MD

• Franken, Gijs AC, Boston Children's Hospital, Boston, Massachusetts, United States

Gijs AC Franken, MS, MSc, PhD

• El Desoky, Sherif Mohamed, King Abdulaziz University, Jeddah, Makkah, Saudi Arabia

Sherif Mohamed El Desoky, MD

• Kari, Jameela Abdulaziz, King Abdulaziz University, Jeddah, Makkah, Saudi Arabia

Jameela Abdulaziz Kari, MD, PhD

• Hildebrandt, Friedhelm, Boston Children's Hospital, Boston, Massachusetts, United States

Friedhelm Hildebrandt, MD

Group or Team Name

• Hildebrandt Lab.

Background

In pediatric patients, the most frequent causes for end stage kidney disease (ESKD) are congenital anomalies of the kidney and urinary tract (CAKUT), followed by glomerulonephritis, steroid-resistant nephrotic syndrome (SRNS), renal ciliopathies and nephrolithiasis/nephrocalcinosis. A significant fraction of these disease entities is due to monogenic causes, ranging from ~10% in CAKUT to about ~55% in renal ciliopathies. Exome sequencing (ES) has revealed numerous disease-causing genes and pathogenic variants in these genes. Nevertheless, continuous efforts are crucial to expand the knowledge on these variants to establish unequivocal diagnoses. In this study, we report ES data from a single Saudi-Arabian center with an underrepresented population. Through this study, we aim to explore potential founder effects and determine specific genotype-phenotype correlations based on clinical diagnoses and genetic ancestry.

Methods

We consolidated 377 families with either SRNS, CAKUT, NPHP and stone disease / tubulopathy. In these families, we performed ES and analyzed the obtained data for variants in established disease genes for the respective diseases. These families were recruited between 2007 – 2023 at King Abdul Aziz University in Jeddah, Saudi Arabia.

Results

In this highly homozygous cohort (homozygosity by descent: 116 Mb (mean), 91 Mb (median)) 163/377 (43%) patients had SRNS, 155/377 (41%) had CAKUT, 36/377 (9.5%) had renal ciliopathies and 23/377 (6%) had stone disease / tubulopathies. Pathogenic variants were identified in 36% of families with SRNS, 18% of families with CAKUT, 75% of families with NPHP, and 61% of families with stone disease.

Conclusion

We identified a genetic cause of kidney disease in 33.6% of patients from a single Saudi-Arabian center. Elucidating prevalent disease genes and disease variants in a defined region and genetic ancestry group can provide important insights into variant pathogenicity assessment, disease management, and prognosis.

Funding

• Government Support – Non-U.S.