Novel TP53RK variants cause varied clinical features of Galloway–Mowat syndrome without nephrotic syndrome in three unrelated Chinese patients
ObjectivesGalloway–Mowat syndrome-4 (GAMOS4) is a very rare renal-neurological disease caused by TP53RK gene mutations. GAMOS4 is characterized by early-onset nephrotic syndrome, microcephaly, and brain anomalies. To date, only nine GAMOS4 cases with detailed clinical data (caused by eight deleterio...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-02-01
|
| Series: | Frontiers in Molecular Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fnmol.2023.1116949/full |
| _version_ | 1797905250459320320 |
|---|---|
| author | Jing Chen Gao-Bo Ye Jin-Rong Huang Min Peng Wei-Yue Gu Pin Xiong Hong-min Zhu |
| author_facet | Jing Chen Gao-Bo Ye Jin-Rong Huang Min Peng Wei-Yue Gu Pin Xiong Hong-min Zhu |
| author_sort | Jing Chen |
| collection | DOAJ |
| description | ObjectivesGalloway–Mowat syndrome-4 (GAMOS4) is a very rare renal-neurological disease caused by TP53RK gene mutations. GAMOS4 is characterized by early-onset nephrotic syndrome, microcephaly, and brain anomalies. To date, only nine GAMOS4 cases with detailed clinical data (caused by eight deleterious variants in TP53RK) have been reported. This study aimed to examine the clinical and genetic characteristics of three unrelated GAMOS4 patients with TP53RK gene compound heterozygous mutations.MethodsWhole-exome sequencing (WES) was used to identify four novel TP53RK variants in three unrelated Chinese children. Clinical characteristics such as biochemical parameters and image findings of patients were also evaluated. Furthermore, four studies of GAMOS4 patients with TP53RK variants were reviewed. In addition, clinical and genetic features were described after a retrospective analysis of clinical symptoms, laboratory data, and genetic test results.ResultsThe three patients showed facial abnormalities, developmental delays, microcephaly, and aberrant cerebral imaging. Furthermore, patient 1 had slight proteinuria, while patient 2 had epilepsy. However, none of the individuals had nephrotic syndrome, and all were alive for more than 3 years of age. This is the first study to assess four variants in the TP53RK gene (NM_033550.4: c.15_16dup/p.A6Efs*29, c.745A > G/p.R249G, c.185G > A/p.R62H, and c.335A > G/p.Y112C).ConclusionThe clinical characteristics of the three children with TP53RK mutations are significantly different from the known GAMOS4 traits, including early nephrotic syndrome and mortality mainly occurring in the first year of life. This study provides insights into the pathogenic TP53RK gene mutation spectrum and clinical phenotypes of GAMOS4. |
| first_indexed | 2024-04-10T10:02:10Z |
| format | Article |
| id | doaj.art-47b3356516e843c4899890dbf4eebeb0 |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-04-10T10:02:10Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-47b3356516e843c4899890dbf4eebeb02023-02-16T06:19:46ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992023-02-011610.3389/fnmol.2023.11169491116949Novel TP53RK variants cause varied clinical features of Galloway–Mowat syndrome without nephrotic syndrome in three unrelated Chinese patientsJing Chen0Gao-Bo Ye1Jin-Rong Huang2Min Peng3Wei-Yue Gu4Pin Xiong5Hong-min Zhu6Pediatric Rehabilitation Medicine, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Pediatrics, The Second Affiliated Hospital of Xi’an Jiaotong University, Xian, ChinaGanzhou Women and Children Health Hospital, Ganzhou, ChinaChigene Beijing Translational Medical Research Center Co., Ltd., Beijing, ChinaChigene Beijing Translational Medical Research Center Co., Ltd., Beijing, ChinaPediatric Rehabilitation Medicine, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaPediatric Rehabilitation Medicine, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaObjectivesGalloway–Mowat syndrome-4 (GAMOS4) is a very rare renal-neurological disease caused by TP53RK gene mutations. GAMOS4 is characterized by early-onset nephrotic syndrome, microcephaly, and brain anomalies. To date, only nine GAMOS4 cases with detailed clinical data (caused by eight deleterious variants in TP53RK) have been reported. This study aimed to examine the clinical and genetic characteristics of three unrelated GAMOS4 patients with TP53RK gene compound heterozygous mutations.MethodsWhole-exome sequencing (WES) was used to identify four novel TP53RK variants in three unrelated Chinese children. Clinical characteristics such as biochemical parameters and image findings of patients were also evaluated. Furthermore, four studies of GAMOS4 patients with TP53RK variants were reviewed. In addition, clinical and genetic features were described after a retrospective analysis of clinical symptoms, laboratory data, and genetic test results.ResultsThe three patients showed facial abnormalities, developmental delays, microcephaly, and aberrant cerebral imaging. Furthermore, patient 1 had slight proteinuria, while patient 2 had epilepsy. However, none of the individuals had nephrotic syndrome, and all were alive for more than 3 years of age. This is the first study to assess four variants in the TP53RK gene (NM_033550.4: c.15_16dup/p.A6Efs*29, c.745A > G/p.R249G, c.185G > A/p.R62H, and c.335A > G/p.Y112C).ConclusionThe clinical characteristics of the three children with TP53RK mutations are significantly different from the known GAMOS4 traits, including early nephrotic syndrome and mortality mainly occurring in the first year of life. This study provides insights into the pathogenic TP53RK gene mutation spectrum and clinical phenotypes of GAMOS4.https://www.frontiersin.org/articles/10.3389/fnmol.2023.1116949/fullTP53RK geneGalloway–Mowat syndromenephrotic syndromeproteinuriaglobal developmental delays |
| spellingShingle | Jing Chen Gao-Bo Ye Jin-Rong Huang Min Peng Wei-Yue Gu Pin Xiong Hong-min Zhu Novel TP53RK variants cause varied clinical features of Galloway–Mowat syndrome without nephrotic syndrome in three unrelated Chinese patients Frontiers in Molecular Neuroscience TP53RK gene Galloway–Mowat syndrome nephrotic syndrome proteinuria global developmental delays |
| title | Novel TP53RK variants cause varied clinical features of Galloway–Mowat syndrome without nephrotic syndrome in three unrelated Chinese patients |
| title_full | Novel TP53RK variants cause varied clinical features of Galloway–Mowat syndrome without nephrotic syndrome in three unrelated Chinese patients |
| title_fullStr | Novel TP53RK variants cause varied clinical features of Galloway–Mowat syndrome without nephrotic syndrome in three unrelated Chinese patients |
| title_full_unstemmed | Novel TP53RK variants cause varied clinical features of Galloway–Mowat syndrome without nephrotic syndrome in three unrelated Chinese patients |
| title_short | Novel TP53RK variants cause varied clinical features of Galloway–Mowat syndrome without nephrotic syndrome in three unrelated Chinese patients |
| title_sort | novel tp53rk variants cause varied clinical features of galloway mowat syndrome without nephrotic syndrome in three unrelated chinese patients |
| topic | TP53RK gene Galloway–Mowat syndrome nephrotic syndrome proteinuria global developmental delays |
| url | https://www.frontiersin.org/articles/10.3389/fnmol.2023.1116949/full |
| work_keys_str_mv | AT jingchen noveltp53rkvariantscausevariedclinicalfeaturesofgallowaymowatsyndromewithoutnephroticsyndromeinthreeunrelatedchinesepatients AT gaoboye noveltp53rkvariantscausevariedclinicalfeaturesofgallowaymowatsyndromewithoutnephroticsyndromeinthreeunrelatedchinesepatients AT jinronghuang noveltp53rkvariantscausevariedclinicalfeaturesofgallowaymowatsyndromewithoutnephroticsyndromeinthreeunrelatedchinesepatients AT minpeng noveltp53rkvariantscausevariedclinicalfeaturesofgallowaymowatsyndromewithoutnephroticsyndromeinthreeunrelatedchinesepatients AT weiyuegu noveltp53rkvariantscausevariedclinicalfeaturesofgallowaymowatsyndromewithoutnephroticsyndromeinthreeunrelatedchinesepatients AT pinxiong noveltp53rkvariantscausevariedclinicalfeaturesofgallowaymowatsyndromewithoutnephroticsyndromeinthreeunrelatedchinesepatients AT hongminzhu noveltp53rkvariantscausevariedclinicalfeaturesofgallowaymowatsyndromewithoutnephroticsyndromeinthreeunrelatedchinesepatients |