Genetics and phenotypic heterogeneity of Galloway–Mowat syndrome
Abstract Galloway–Mowat syndrome (GAMOS) is a rare autosomal recessive genetic disorder that is underrecognized. The phenotype is heterogeneous, but it is now widely accepted that early-onset nephrotic syndrome (SRNS) and microcephaly with brain malformation are characteristic features of Galloway–M...
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BMC
2025-06-01
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| Series: | Cell Communication and Signaling |
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| Online Access: | https://doi.org/10.1186/s12964-025-02307-8 |
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| author | Limin Huang Yanfei Wang Yingying Zhang Haidong Fu Jianhua Mao |
| author_facet | Limin Huang Yanfei Wang Yingying Zhang Haidong Fu Jianhua Mao |
| author_sort | Limin Huang |
| collection | DOAJ |
| description | Abstract Galloway–Mowat syndrome (GAMOS) is a rare autosomal recessive genetic disorder that is underrecognized. The phenotype is heterogeneous, but it is now widely accepted that early-onset nephrotic syndrome (SRNS) and microcephaly with brain malformation are characteristic features of Galloway–Mowat syndrome. Although the five subunits that encode the KEOPS complex, OSGEP/TP53RK/TPRKB/LAGE3/GON7, are known to cause Galloway–Mowat syndrome, the mutation of the WDR73, WDR4, NUP107, NUP133, and PRDM15 genes can lead to Galloway–Mowat syndrome, which makes the diagnosis more challenging. This review outlines current knowledge regarding Galloway–Mowat syndrome from another perspective. Starting from the history of Galloway–Mowat syndrome and reviewing the clinical details of patients with and without genetic traits, we discuss the phenotypic and genetic heterogeneity of the disease. We pay particular attention to all confounding clinical signs and symptoms that may lead to misdiagnosis. Indeed, some patients with Galloway–Mowat syndrome have a clinical condition of nephrotic range proteinuria, with or without hematuria, such as glomerular disease or chronic kidney disease of unknown origin. Although glomerular injury is frequently documented in biopsies of patients with Galloway–Mowat syndrome, there is currently no reliable evidence that renal biopsy has diagnostic or prognostic value. We reviewed published histopathological reports of renal tubule and glomerular injury in these patients and discussed the current knowledge on the role of genes that contribute to the onset of Galloway–Mowat syndrome in glomerular function. |
| format | Article |
| id | doaj-art-1b9f229bfedd4dcd855bfac779f5d805 |
| institution | OA Journals |
| issn | 1478-811X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
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| series | Cell Communication and Signaling |
| spelling | doaj-art-1b9f229bfedd4dcd855bfac779f5d8052025-08-20T02:10:31ZengBMCCell Communication and Signaling1478-811X2025-06-0123111010.1186/s12964-025-02307-8Genetics and phenotypic heterogeneity of Galloway–Mowat syndromeLimin Huang0Yanfei Wang1Yingying Zhang2Haidong Fu3Jianhua Mao4Department of Nephrology, Children’s Hospital, National clinical research center for child health, Zhejiang University School of MedicineChildren’s Hospital of Fudan UniversityDepartment of Pediatrics, Clinical Center of Pediatric Nephrology of Henan Province, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Nephrology, Children’s Hospital, National clinical research center for child health, Zhejiang University School of MedicineDepartment of Nephrology, Children’s Hospital, National clinical research center for child health, Zhejiang University School of MedicineAbstract Galloway–Mowat syndrome (GAMOS) is a rare autosomal recessive genetic disorder that is underrecognized. The phenotype is heterogeneous, but it is now widely accepted that early-onset nephrotic syndrome (SRNS) and microcephaly with brain malformation are characteristic features of Galloway–Mowat syndrome. Although the five subunits that encode the KEOPS complex, OSGEP/TP53RK/TPRKB/LAGE3/GON7, are known to cause Galloway–Mowat syndrome, the mutation of the WDR73, WDR4, NUP107, NUP133, and PRDM15 genes can lead to Galloway–Mowat syndrome, which makes the diagnosis more challenging. This review outlines current knowledge regarding Galloway–Mowat syndrome from another perspective. Starting from the history of Galloway–Mowat syndrome and reviewing the clinical details of patients with and without genetic traits, we discuss the phenotypic and genetic heterogeneity of the disease. We pay particular attention to all confounding clinical signs and symptoms that may lead to misdiagnosis. Indeed, some patients with Galloway–Mowat syndrome have a clinical condition of nephrotic range proteinuria, with or without hematuria, such as glomerular disease or chronic kidney disease of unknown origin. Although glomerular injury is frequently documented in biopsies of patients with Galloway–Mowat syndrome, there is currently no reliable evidence that renal biopsy has diagnostic or prognostic value. We reviewed published histopathological reports of renal tubule and glomerular injury in these patients and discussed the current knowledge on the role of genes that contribute to the onset of Galloway–Mowat syndrome in glomerular function.https://doi.org/10.1186/s12964-025-02307-8Galloway–Mowat syndromeWDR73KEOPS complexPhenotypic heterogeneity |
| spellingShingle | Limin Huang Yanfei Wang Yingying Zhang Haidong Fu Jianhua Mao Genetics and phenotypic heterogeneity of Galloway–Mowat syndrome Cell Communication and Signaling Galloway–Mowat syndrome WDR73 KEOPS complex Phenotypic heterogeneity |
| title | Genetics and phenotypic heterogeneity of Galloway–Mowat syndrome |
| title_full | Genetics and phenotypic heterogeneity of Galloway–Mowat syndrome |
| title_fullStr | Genetics and phenotypic heterogeneity of Galloway–Mowat syndrome |
| title_full_unstemmed | Genetics and phenotypic heterogeneity of Galloway–Mowat syndrome |
| title_short | Genetics and phenotypic heterogeneity of Galloway–Mowat syndrome |
| title_sort | genetics and phenotypic heterogeneity of galloway mowat syndrome |
| topic | Galloway–Mowat syndrome WDR73 KEOPS complex Phenotypic heterogeneity |
| url | https://doi.org/10.1186/s12964-025-02307-8 |
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