Frontiers in Genetics (Jun 2022)
Genomic, Proteomic, and Phenotypic Spectrum of Novel O-Sialoglycoprotein Endopeptidase Variant in Four Affected Individuals With Galloway-Mowat Syndrome
- Malak Ali Alghamdi,
- Malak Ali Alghamdi,
- Hicham Benabdelkamel,
- Afshan Masood,
- Narjes Saheb Sharif-Askari,
- Mahmood Y. Hachim,
- Hamad Alsheikh,
- Muddathir H. Hamad,
- Mustafa A. Salih,
- Fahad A. Bashiri,
- Fahad A. Bashiri,
- Khalid Alhasan,
- Khalid Alhasan,
- Khalid Alhasan,
- Tarek Kashour,
- Pilar Guatibonza Moreno,
- Sabine Schröder,
- Vasiliki Karageorgou,
- Aida M. Bertoli-Avella,
- Hisham Alkhalidi,
- Dima Z. Jamjoom,
- Ibrahim A. Alorainy,
- Assim A. Alfadda,
- Assim A. Alfadda,
- Assim A. Alfadda,
- Rabih Halwani
Affiliations
- Malak Ali Alghamdi
- Pediatric Department, College of Medicine, King Saud University, Riyadh, Saudi Arabia
- Malak Ali Alghamdi
- Medical Genetics Division, Department of Pediatrics, King Saud University, Riyadh, Saudi Arabia
- Hicham Benabdelkamel
- Proteomics Resource Unit, Obesity Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia
- Afshan Masood
- Proteomics Resource Unit, Obesity Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia
- Narjes Saheb Sharif-Askari
- Sharjah Institute for Medical Research, University of Sharjah, Dubai, United Arab Emirates
- Mahmood Y. Hachim
- College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates
- Hamad Alsheikh
- Neurology Division, Department of Pediatrics, King Saud University, Riyadh, Saudi Arabia
- Muddathir H. Hamad
- Neurology Division, Department of Pediatrics, King Saud University, Riyadh, Saudi Arabia
- Mustafa A. Salih
- Pediatric Department, College of Medicine, King Saud University, Riyadh, Saudi Arabia
- Fahad A. Bashiri
- Pediatric Department, College of Medicine, King Saud University, Riyadh, Saudi Arabia
- Fahad A. Bashiri
- Neurology Division, Department of Pediatrics, King Saud University, Riyadh, Saudi Arabia
- Khalid Alhasan
- Pediatric Department, College of Medicine, King Saud University, Riyadh, Saudi Arabia
- Khalid Alhasan
- Nephology Division, Department of Pediatrics, King Saud University, Riyadh, Saudi Arabia
- Khalid Alhasan
- Pediatric Kidney Transplant Division,Organ Transplant Center, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
- Tarek Kashour
- Cardiology Department, College of Medicine, King Saud University, Riyadh, Saudi Arabia
- Pilar Guatibonza Moreno
- 0CENTOGENE GmbH, Rostock, Germany
- Sabine Schröder
- 0CENTOGENE GmbH, Rostock, Germany
- Vasiliki Karageorgou
- 0CENTOGENE GmbH, Rostock, Germany
- Aida M. Bertoli-Avella
- 0CENTOGENE GmbH, Rostock, Germany
- Hisham Alkhalidi
- 1Pathology Department, College of Medicine, King Saud University, Riyadh, Saudi Arabia
- Dima Z. Jamjoom
- 2Radiology and Medical Imaging Department, College of Medicine, King Saud University, Riyadh, Saudi Arabia
- Ibrahim A. Alorainy
- 2Radiology and Medical Imaging Department, College of Medicine, King Saud University, Riyadh, Saudi Arabia
- Assim A. Alfadda
- Proteomics Resource Unit, Obesity Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia
- Assim A. Alfadda
- 3Department of Medicine, College of Medicine and King Saud Medical City, King Saud University, Riyadh, Saudi Arabia
- Assim A. Alfadda
- 4Strategic Center for Diabetes Research, College of Medicine, King Saud University, Riyadh, Saudi Arabia
- Rabih Halwani
- 5Department of Clinical Sciences, College of Medicine, Sharjah Institute for Medical Research (SIMR), University of Sharjah, Sharjah, United Arab Emirates
- DOI
- https://doi.org/10.3389/fgene.2022.806190
- Journal volume & issue
-
Vol. 13
Abstract
Galloway-Mowat syndrome is a rare autosomal recessive disease characterized by a unique combination of renal and neurological manifestations, including early-onset steroid-resistant nephrotic syndrome, microcephaly, psychomotor delay, and gyral abnormalities of the brain. Most patients die during early childhood. Here, we identified a novel homozygous O-sialoglycoprotein endopeptidase (OSGEP) variant, NM_017807.3:c.973C>G (p.Arg325Gly), in four affected individuals in an extended consanguineous family from Saudi Arabia. We have described the detailed clinical characterization, brain imaging results, and muscle biopsy findings. The described phenotype varied from embryonic lethality to early pregnancy loss or death at the age of 9. Renal disease is often the cause of death. Protein modeling of this OSGEP variant confirmed its pathogenicity. In addition, proteomic analysis of the affected patients proposed a link between the KEOPS complex function and human pathology and suggested potential pathogenic mechanisms.
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