Genomic, Proteomic, and Phenotypic Spectrum of Novel O-Sialoglycoprotein Endopeptidase Variant in Four Affected Individuals With Galloway-Mowat Syndrome
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 ea...
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.806190/full |
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| author | 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 |
| author_facet | 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 |
| author_sort | Malak Ali Alghamdi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T16:16:15Z |
| format | Article |
| id | doaj.art-8db6644c11c4473ea480bba4e547fa50 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-12T16:16:15Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-8db6644c11c4473ea480bba4e547fa502022-12-22T00:19:05ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-06-011310.3389/fgene.2022.806190806190Genomic, Proteomic, and Phenotypic Spectrum of Novel O-Sialoglycoprotein Endopeptidase Variant in Four Affected Individuals With Galloway-Mowat SyndromeMalak Ali Alghamdi0Malak Ali Alghamdi1Hicham Benabdelkamel2Afshan Masood3Narjes Saheb Sharif-Askari4Mahmood Y. Hachim5Hamad Alsheikh6Muddathir H. Hamad7Mustafa A. Salih8Fahad A. Bashiri9Fahad A. Bashiri10Khalid Alhasan11Khalid Alhasan12Khalid Alhasan13Tarek Kashour14Pilar Guatibonza Moreno15Sabine Schröder16Vasiliki Karageorgou17Aida M. Bertoli-Avella18Hisham Alkhalidi19Dima Z. Jamjoom20Ibrahim A. Alorainy21Assim A. Alfadda22Assim A. Alfadda23Assim A. Alfadda24Rabih Halwani25Pediatric Department, College of Medicine, King Saud University, Riyadh, Saudi ArabiaMedical Genetics Division, Department of Pediatrics, King Saud University, Riyadh, Saudi ArabiaProteomics Resource Unit, Obesity Research Center, College of Medicine, King Saud University, Riyadh, Saudi ArabiaProteomics Resource Unit, Obesity Research Center, College of Medicine, King Saud University, Riyadh, Saudi ArabiaSharjah Institute for Medical Research, University of Sharjah, Dubai, United Arab EmiratesCollege of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab EmiratesNeurology Division, Department of Pediatrics, King Saud University, Riyadh, Saudi ArabiaNeurology Division, Department of Pediatrics, King Saud University, Riyadh, Saudi ArabiaPediatric Department, College of Medicine, King Saud University, Riyadh, Saudi ArabiaPediatric Department, College of Medicine, King Saud University, Riyadh, Saudi ArabiaNeurology Division, Department of Pediatrics, King Saud University, Riyadh, Saudi ArabiaPediatric Department, College of Medicine, King Saud University, Riyadh, Saudi ArabiaNephology Division, Department of Pediatrics, King Saud University, Riyadh, Saudi ArabiaPediatric Kidney Transplant Division,Organ Transplant Center, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi ArabiaCardiology Department, College of Medicine, King Saud University, Riyadh, Saudi Arabia0CENTOGENE GmbH, Rostock, Germany0CENTOGENE GmbH, Rostock, Germany0CENTOGENE GmbH, Rostock, Germany0CENTOGENE GmbH, Rostock, Germany1Pathology Department, College of Medicine, King Saud University, Riyadh, Saudi Arabia2Radiology and Medical Imaging Department, College of Medicine, King Saud University, Riyadh, Saudi Arabia2Radiology and Medical Imaging Department, College of Medicine, King Saud University, Riyadh, Saudi ArabiaProteomics Resource Unit, Obesity Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia3Department of Medicine, College of Medicine and King Saud Medical City, King Saud University, Riyadh, Saudi Arabia4Strategic Center for Diabetes Research, College of Medicine, King Saud University, Riyadh, Saudi Arabia5Department of Clinical Sciences, College of Medicine, Sharjah Institute for Medical Research (SIMR), University of Sharjah, Sharjah, United Arab EmiratesGalloway-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.https://www.frontiersin.org/articles/10.3389/fgene.2022.806190/fullGalloway-Mowat syndromesteroid-resistant nephrotic syndromeGAMOSproteomicKEOPS complex |
| spellingShingle | 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 Genomic, Proteomic, and Phenotypic Spectrum of Novel O-Sialoglycoprotein Endopeptidase Variant in Four Affected Individuals With Galloway-Mowat Syndrome Frontiers in Genetics Galloway-Mowat syndrome steroid-resistant nephrotic syndrome GAMOS proteomic KEOPS complex |
| title | Genomic, Proteomic, and Phenotypic Spectrum of Novel O-Sialoglycoprotein Endopeptidase Variant in Four Affected Individuals With Galloway-Mowat Syndrome |
| title_full | Genomic, Proteomic, and Phenotypic Spectrum of Novel O-Sialoglycoprotein Endopeptidase Variant in Four Affected Individuals With Galloway-Mowat Syndrome |
| title_fullStr | Genomic, Proteomic, and Phenotypic Spectrum of Novel O-Sialoglycoprotein Endopeptidase Variant in Four Affected Individuals With Galloway-Mowat Syndrome |
| title_full_unstemmed | Genomic, Proteomic, and Phenotypic Spectrum of Novel O-Sialoglycoprotein Endopeptidase Variant in Four Affected Individuals With Galloway-Mowat Syndrome |
| title_short | Genomic, Proteomic, and Phenotypic Spectrum of Novel O-Sialoglycoprotein Endopeptidase Variant in Four Affected Individuals With Galloway-Mowat Syndrome |
| title_sort | genomic proteomic and phenotypic spectrum of novel o sialoglycoprotein endopeptidase variant in four affected individuals with galloway mowat syndrome |
| topic | Galloway-Mowat syndrome steroid-resistant nephrotic syndrome GAMOS proteomic KEOPS complex |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.806190/full |
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