Case report: expanding the phenotype of ARHGEF17 mutations from increased intracranial aneurysm risk to a neurodevelopmental disease
RhoGTPase regulators play a key role in the development of the nervous system, and their dysfunction can result in brain malformation and associated disorders. Several guanine nucleotide exchange factors (GEF) have been linked to neurodevelopmental disorders. In line with this, ARHGEF17 has been rec...
| Main Authors: | , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
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2023
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| Online Access: | https://hdl.handle.net/10356/171041 |
| _version_ | 1811692965441044480 |
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| author | Ravindran, Ethiraj Ullah, Noor Mani, Shyamala Chew, Elaine Guo Yan Tandiono, Moses Foo, Jia Nee Khor, Chiea Chuen Kaindl, Angela M. Siddiqi, Saima |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) Ravindran, Ethiraj Ullah, Noor Mani, Shyamala Chew, Elaine Guo Yan Tandiono, Moses Foo, Jia Nee Khor, Chiea Chuen Kaindl, Angela M. Siddiqi, Saima |
| author_sort | Ravindran, Ethiraj |
| collection | NTU |
| description | RhoGTPase regulators play a key role in the development of the nervous system, and their dysfunction can result in brain malformation and associated disorders. Several guanine nucleotide exchange factors (GEF) have been linked to neurodevelopmental disorders. In line with this, ARHGEF17 has been recently linked as a risk gene to intracranial aneurysms. Here we report siblings of a consanguineous Pakistani family with biallelic variants in the ARHGEF17 gene associated with a neurodevelopmental disorder with intellectual disability, speech delay and motor dysfunction but not aneurysms. Cranial MRI performed in one patient revealed generalized brain atrophy with an enlarged ventricular system, thin corpus callosum and microcephaly. Whole exome sequencing followed by Sanger sequencing in two of the affected individuals revealed a homozygous missense variant (g.11:73021307, c.1624C>T (NM_014786.4), p.R542W) in the ARHGEF17 gene. This variant is in a highly conserved DCLK1 phosphorylation consensus site (I/L/V/F/M]RRXX[pS/pT][I/L/M/V/F) of the protein. Our report expands the phenotypic spectrum of ARHGEF17 variants from increased intracranial aneurysm risk to neurodevelopmental disease and thereby add ARHGEF17 to the list of GEF genes involved in neurodevelopmental disorders. |
| first_indexed | 2024-10-01T06:44:10Z |
| format | Journal Article |
| id | ntu-10356/171041 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T06:44:10Z |
| publishDate | 2023 |
| record_format | dspace |
| spelling | ntu-10356/1710412023-10-15T15:38:32Z Case report: expanding the phenotype of ARHGEF17 mutations from increased intracranial aneurysm risk to a neurodevelopmental disease Ravindran, Ethiraj Ullah, Noor Mani, Shyamala Chew, Elaine Guo Yan Tandiono, Moses Foo, Jia Nee Khor, Chiea Chuen Kaindl, Angela M. Siddiqi, Saima Lee Kong Chian School of Medicine (LKCMedicine) Genome Institute of Singapore, A*STAR Science::Medicine Neurodevelopmental Disorder Microcephal RhoGTPase regulators play a key role in the development of the nervous system, and their dysfunction can result in brain malformation and associated disorders. Several guanine nucleotide exchange factors (GEF) have been linked to neurodevelopmental disorders. In line with this, ARHGEF17 has been recently linked as a risk gene to intracranial aneurysms. Here we report siblings of a consanguineous Pakistani family with biallelic variants in the ARHGEF17 gene associated with a neurodevelopmental disorder with intellectual disability, speech delay and motor dysfunction but not aneurysms. Cranial MRI performed in one patient revealed generalized brain atrophy with an enlarged ventricular system, thin corpus callosum and microcephaly. Whole exome sequencing followed by Sanger sequencing in two of the affected individuals revealed a homozygous missense variant (g.11:73021307, c.1624C>T (NM_014786.4), p.R542W) in the ARHGEF17 gene. This variant is in a highly conserved DCLK1 phosphorylation consensus site (I/L/V/F/M]RRXX[pS/pT][I/L/M/V/F) of the protein. Our report expands the phenotypic spectrum of ARHGEF17 variants from increased intracranial aneurysm risk to neurodevelopmental disease and thereby add ARHGEF17 to the list of GEF genes involved in neurodevelopmental disorders. Agency for Science, Technology and Research (A*STAR) National Research Foundation (NRF) Published version We acknowledge the funding resources for this study: The genetic analysis was supported by the Agency for Science, Technology and Research, Singapore (to CK) and a Singapore National Research Foundation Fellowship (NRFNRFF2016-03; to JF). Family and clinical data collection was supported by departmental grant (IBGE) (SS). Further funding includes the German Research Foundation (SFB665, SFB1315, FOR3004, AK), the Sonnenfeld Stiftung (AK), the Berlin Institute of Health (BIH, CRG1, AK) and the Charité (AK, ER, and SM). 2023-10-10T07:11:39Z 2023-10-10T07:11:39Z 2022 Journal Article Ravindran, E., Ullah, N., Mani, S., Chew, E. G. Y., Tandiono, M., Foo, J. N., Khor, C. C., Kaindl, A. M. & Siddiqi, S. (2022). Case report: expanding the phenotype of ARHGEF17 mutations from increased intracranial aneurysm risk to a neurodevelopmental disease. Frontiers in Neurology, 13, 1017654-. https://dx.doi.org/10.3389/fneur.2022.1017654 1664-2295 https://hdl.handle.net/10356/171041 10.3389/fneur.2022.1017654 36341116 2-s2.0-85141159110 13 1017654 en NRF-NRFF2016-03 Frontiers in Neurology © 2022 Ravindran, Ullah, Mani, Chew, Tandiono, Foo, Khor, Kaindl and Siddiqi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. application/pdf |
| spellingShingle | Science::Medicine Neurodevelopmental Disorder Microcephal Ravindran, Ethiraj Ullah, Noor Mani, Shyamala Chew, Elaine Guo Yan Tandiono, Moses Foo, Jia Nee Khor, Chiea Chuen Kaindl, Angela M. Siddiqi, Saima Case report: expanding the phenotype of ARHGEF17 mutations from increased intracranial aneurysm risk to a neurodevelopmental disease |
| title | Case report: expanding the phenotype of ARHGEF17 mutations from increased intracranial aneurysm risk to a neurodevelopmental disease |
| title_full | Case report: expanding the phenotype of ARHGEF17 mutations from increased intracranial aneurysm risk to a neurodevelopmental disease |
| title_fullStr | Case report: expanding the phenotype of ARHGEF17 mutations from increased intracranial aneurysm risk to a neurodevelopmental disease |
| title_full_unstemmed | Case report: expanding the phenotype of ARHGEF17 mutations from increased intracranial aneurysm risk to a neurodevelopmental disease |
| title_short | Case report: expanding the phenotype of ARHGEF17 mutations from increased intracranial aneurysm risk to a neurodevelopmental disease |
| title_sort | case report expanding the phenotype of arhgef17 mutations from increased intracranial aneurysm risk to a neurodevelopmental disease |
| topic | Science::Medicine Neurodevelopmental Disorder Microcephal |
| url | https://hdl.handle.net/10356/171041 |
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