Case report: Phenotype expansion and analysis of TRIO and CNKSR2 variations
IntroductionTRIO and CNKSR2 have been demonstrated as the important regulators of RAC1. TRIO is a guanine exchange factor (GEF) and promotes RAC1 activity by accelerating the GDP to GTP exchange. CNKSR2 is a scaffold and adaptor protein and helps to maintain Rac1 GTP/GDP levels at a concentration co...
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| Format: | Article |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2022.948877/full |
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| author | Yuefang Liu Zhe Liang Weili Cai Qixiang Shao Qixiang Shao Qiong Pan |
| author_facet | Yuefang Liu Zhe Liang Weili Cai Qixiang Shao Qixiang Shao Qiong Pan |
| author_sort | Yuefang Liu |
| collection | DOAJ |
| description | IntroductionTRIO and CNKSR2 have been demonstrated as the important regulators of RAC1. TRIO is a guanine exchange factor (GEF) and promotes RAC1 activity by accelerating the GDP to GTP exchange. CNKSR2 is a scaffold and adaptor protein and helps to maintain Rac1 GTP/GDP levels at a concentration conducive for dendritic spines formation. Dysregulated RAC1 activity causes synaptic function defects leading to neurodevelopmental disorders (NDDs), which manifest as intellectual disability, learning difficulties, and language disorders.Case presentationHere, we reported two cases with TRIO variation from one family and three cases with CNKSR2 variation from another family. The family with TRIO variation carries a novel heterozygous frameshift variant c.3506delG (p. Gly1169AlafsTer11), where a prenatal case and an apparently asymptomatic carrier mother with only enlarged left lateral ventricles were firstly reported. On the other hand, the CNKSR2 family carries a novel hemizygous non-sense variant c.1282C>T (p. Arg428*). Concurrently, we identified a novel phenotype never reported in known pathogenic CNKSR2 variants, that hydrocephalus and widening lateral ventricle in a 6-year-old male of this family. Furthermore, the genotype–phenotype relationship for TRIO, CNKSR2, and RAC1 was explored through a literature review.ConclusionThe novel variants and unique clinical features of these two pedigrees will help expand our understanding of the genetic and phenotypic profile of TRIO- and CNKSR2-related diseases. |
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| id | doaj.art-d250f16de7d5447e9d3949c4bf94e7b9 |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-04-14T02:18:05Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-d250f16de7d5447e9d3949c4bf94e7b92022-12-22T02:18:08ZengFrontiers Media S.A.Frontiers in Neurology1664-22952022-08-011310.3389/fneur.2022.948877948877Case report: Phenotype expansion and analysis of TRIO and CNKSR2 variationsYuefang Liu0Zhe Liang1Weili Cai2Qixiang Shao3Qixiang Shao4Qiong Pan5Department of Clinical Genetics, Huai'an Maternity and Child Clinical College of Xuzhou Medical University, Huai'an, ChinaDepartment of Clinical Genetics, Huai'an Maternity and Child Clinical College of Xuzhou Medical University, Huai'an, ChinaSchool of Medical Science and Laboratory Medicine, Jiangsu College of Nursing, Institute of Medical Genetics and Reproductive Immunity, Huai'an, ChinaSchool of Medical Science and Laboratory Medicine, Jiangsu College of Nursing, Institute of Medical Genetics and Reproductive Immunity, Huai'an, ChinaJiangsu Key Laboratory of Medical Science and Laboratory Medicine, Department of Immunology, School of Medicine, Reproductive Sciences Institute, Jiangsu University, Zhenjiang, ChinaDepartment of Clinical Genetics, Huai'an Maternity and Child Clinical College of Xuzhou Medical University, Huai'an, ChinaIntroductionTRIO and CNKSR2 have been demonstrated as the important regulators of RAC1. TRIO is a guanine exchange factor (GEF) and promotes RAC1 activity by accelerating the GDP to GTP exchange. CNKSR2 is a scaffold and adaptor protein and helps to maintain Rac1 GTP/GDP levels at a concentration conducive for dendritic spines formation. Dysregulated RAC1 activity causes synaptic function defects leading to neurodevelopmental disorders (NDDs), which manifest as intellectual disability, learning difficulties, and language disorders.Case presentationHere, we reported two cases with TRIO variation from one family and three cases with CNKSR2 variation from another family. The family with TRIO variation carries a novel heterozygous frameshift variant c.3506delG (p. Gly1169AlafsTer11), where a prenatal case and an apparently asymptomatic carrier mother with only enlarged left lateral ventricles were firstly reported. On the other hand, the CNKSR2 family carries a novel hemizygous non-sense variant c.1282C>T (p. Arg428*). Concurrently, we identified a novel phenotype never reported in known pathogenic CNKSR2 variants, that hydrocephalus and widening lateral ventricle in a 6-year-old male of this family. Furthermore, the genotype–phenotype relationship for TRIO, CNKSR2, and RAC1 was explored through a literature review.ConclusionThe novel variants and unique clinical features of these two pedigrees will help expand our understanding of the genetic and phenotypic profile of TRIO- and CNKSR2-related diseases.https://www.frontiersin.org/articles/10.3389/fneur.2022.948877/fullTRIOCNKSR2RAC1case reportneurodevelopmental disorders |
| spellingShingle | Yuefang Liu Zhe Liang Weili Cai Qixiang Shao Qixiang Shao Qiong Pan Case report: Phenotype expansion and analysis of TRIO and CNKSR2 variations Frontiers in Neurology TRIO CNKSR2 RAC1 case report neurodevelopmental disorders |
| title | Case report: Phenotype expansion and analysis of TRIO and CNKSR2 variations |
| title_full | Case report: Phenotype expansion and analysis of TRIO and CNKSR2 variations |
| title_fullStr | Case report: Phenotype expansion and analysis of TRIO and CNKSR2 variations |
| title_full_unstemmed | Case report: Phenotype expansion and analysis of TRIO and CNKSR2 variations |
| title_short | Case report: Phenotype expansion and analysis of TRIO and CNKSR2 variations |
| title_sort | case report phenotype expansion and analysis of trio and cnksr2 variations |
| topic | TRIO CNKSR2 RAC1 case report neurodevelopmental disorders |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2022.948877/full |
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