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Pancytopenia, Recurrent Infection, Poor Wound Healing, Heterotopia of the Brain Probably Associated with A Candidate Novel de Novo CDC42 Gene Defect: Expanding the Molecular and Phenotypic Spectrum

CDC42 (cell division cycle protein 42) belongs to the Rho GTPase family that is known to control the signaling axis that regulates several cellular functions, including cell cycle progression, migration, and proliferation. However, the functional characterization of the CDC42 gene in mammalian physi...

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Autores principales: Asiri, Abdulaziz, Alwadaani, Deemah, Umair, Muhammad, Alhamoudi, Kheloud M., Almuhanna, Mohammed H., Nasir, Abdul, Alrfaei, Bahauddeen M., Al Tuwaijri, Abeer, Barhoumi, Tlili, Alyafee, Yusra, Almuzzaini, Bader, Aldrees, Mohammed, Ballow, Mariam, Alayyar, Latifah, Al Abdulrahman, Abdulkareem, Alhaidan, Yazeid, Al Ghasham, Nahlah, Al-Ajaji, Sulaiman, Alsalamah, Mohammad, Al Suwairi, Wafa, Alfadhel, Majid
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923796/
https://www.ncbi.nlm.nih.gov/pubmed/33672558
http://dx.doi.org/10.3390/genes12020294
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author Asiri, Abdulaziz
Alwadaani, Deemah
Umair, Muhammad
Alhamoudi, Kheloud M.
Almuhanna, Mohammed H.
Nasir, Abdul
Alrfaei, Bahauddeen M.
Al Tuwaijri, Abeer
Barhoumi, Tlili
Alyafee, Yusra
Almuzzaini, Bader
Aldrees, Mohammed
Ballow, Mariam
Alayyar, Latifah
Al Abdulrahman, Abdulkareem
Alhaidan, Yazeid
Al Ghasham, Nahlah
Al-Ajaji, Sulaiman
Alsalamah, Mohammad
Al Suwairi, Wafa
Alfadhel, Majid
author_facet Asiri, Abdulaziz
Alwadaani, Deemah
Umair, Muhammad
Alhamoudi, Kheloud M.
Almuhanna, Mohammed H.
Nasir, Abdul
Alrfaei, Bahauddeen M.
Al Tuwaijri, Abeer
Barhoumi, Tlili
Alyafee, Yusra
Almuzzaini, Bader
Aldrees, Mohammed
Ballow, Mariam
Alayyar, Latifah
Al Abdulrahman, Abdulkareem
Alhaidan, Yazeid
Al Ghasham, Nahlah
Al-Ajaji, Sulaiman
Alsalamah, Mohammad
Al Suwairi, Wafa
Alfadhel, Majid
author_sort Asiri, Abdulaziz
collection PubMed
description CDC42 (cell division cycle protein 42) belongs to the Rho GTPase family that is known to control the signaling axis that regulates several cellular functions, including cell cycle progression, migration, and proliferation. However, the functional characterization of the CDC42 gene in mammalian physiology remains largely unclear. Here, we report the genetic and functional characterization of a non-consanguineous Saudi family with a single affected individual. Clinical examinations revealed poor wound healing, heterotopia of the brain, pancytopenia, and recurrent infections. Whole exome sequencing revealed a de novo missense variant (c.101C > A, p.Pro34Gln) in the CDC42 gene. The functional assays revealed a substantial reduction in the growth and motility of the patient cells as compared to the normal cells control. Homology three-dimensional (3-D) modeling of CDC42 revealed that the Pro34 is important for the proper protein secondary structure. In conclusion, we report a candidate disease-causing variant, which requires further confirmation for the etiology of CDC42 pathogenesis. This represents the first case from the Saudi population. The current study adds to the spectrum of mutations in the CDC42 gene that might help in genetic counseling and contributes to the CDC42-related genetic and functional characterization. However, further studies into the molecular mechanisms that are involved are needed in order to determine the role of the CDC42 gene associated with aberrant cell migration and immune response.
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spelling pubmed-79237962021-03-03 Pancytopenia, Recurrent Infection, Poor Wound Healing, Heterotopia of the Brain Probably Associated with A Candidate Novel de Novo CDC42 Gene Defect: Expanding the Molecular and Phenotypic Spectrum Asiri, Abdulaziz Alwadaani, Deemah Umair, Muhammad Alhamoudi, Kheloud M. Almuhanna, Mohammed H. Nasir, Abdul Alrfaei, Bahauddeen M. Al Tuwaijri, Abeer Barhoumi, Tlili Alyafee, Yusra Almuzzaini, Bader Aldrees, Mohammed Ballow, Mariam Alayyar, Latifah Al Abdulrahman, Abdulkareem Alhaidan, Yazeid Al Ghasham, Nahlah Al-Ajaji, Sulaiman Alsalamah, Mohammad Al Suwairi, Wafa Alfadhel, Majid Genes (Basel) Article CDC42 (cell division cycle protein 42) belongs to the Rho GTPase family that is known to control the signaling axis that regulates several cellular functions, including cell cycle progression, migration, and proliferation. However, the functional characterization of the CDC42 gene in mammalian physiology remains largely unclear. Here, we report the genetic and functional characterization of a non-consanguineous Saudi family with a single affected individual. Clinical examinations revealed poor wound healing, heterotopia of the brain, pancytopenia, and recurrent infections. Whole exome sequencing revealed a de novo missense variant (c.101C > A, p.Pro34Gln) in the CDC42 gene. The functional assays revealed a substantial reduction in the growth and motility of the patient cells as compared to the normal cells control. Homology three-dimensional (3-D) modeling of CDC42 revealed that the Pro34 is important for the proper protein secondary structure. In conclusion, we report a candidate disease-causing variant, which requires further confirmation for the etiology of CDC42 pathogenesis. This represents the first case from the Saudi population. The current study adds to the spectrum of mutations in the CDC42 gene that might help in genetic counseling and contributes to the CDC42-related genetic and functional characterization. However, further studies into the molecular mechanisms that are involved are needed in order to determine the role of the CDC42 gene associated with aberrant cell migration and immune response. MDPI 2021-02-20 /pmc/articles/PMC7923796/ /pubmed/33672558 http://dx.doi.org/10.3390/genes12020294 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Asiri, Abdulaziz
Alwadaani, Deemah
Umair, Muhammad
Alhamoudi, Kheloud M.
Almuhanna, Mohammed H.
Nasir, Abdul
Alrfaei, Bahauddeen M.
Al Tuwaijri, Abeer
Barhoumi, Tlili
Alyafee, Yusra
Almuzzaini, Bader
Aldrees, Mohammed
Ballow, Mariam
Alayyar, Latifah
Al Abdulrahman, Abdulkareem
Alhaidan, Yazeid
Al Ghasham, Nahlah
Al-Ajaji, Sulaiman
Alsalamah, Mohammad
Al Suwairi, Wafa
Alfadhel, Majid
Pancytopenia, Recurrent Infection, Poor Wound Healing, Heterotopia of the Brain Probably Associated with A Candidate Novel de Novo CDC42 Gene Defect: Expanding the Molecular and Phenotypic Spectrum
title Pancytopenia, Recurrent Infection, Poor Wound Healing, Heterotopia of the Brain Probably Associated with A Candidate Novel de Novo CDC42 Gene Defect: Expanding the Molecular and Phenotypic Spectrum
title_full Pancytopenia, Recurrent Infection, Poor Wound Healing, Heterotopia of the Brain Probably Associated with A Candidate Novel de Novo CDC42 Gene Defect: Expanding the Molecular and Phenotypic Spectrum
title_fullStr Pancytopenia, Recurrent Infection, Poor Wound Healing, Heterotopia of the Brain Probably Associated with A Candidate Novel de Novo CDC42 Gene Defect: Expanding the Molecular and Phenotypic Spectrum
title_full_unstemmed Pancytopenia, Recurrent Infection, Poor Wound Healing, Heterotopia of the Brain Probably Associated with A Candidate Novel de Novo CDC42 Gene Defect: Expanding the Molecular and Phenotypic Spectrum
title_short Pancytopenia, Recurrent Infection, Poor Wound Healing, Heterotopia of the Brain Probably Associated with A Candidate Novel de Novo CDC42 Gene Defect: Expanding the Molecular and Phenotypic Spectrum
title_sort pancytopenia, recurrent infection, poor wound healing, heterotopia of the brain probably associated with a candidate novel de novo cdc42 gene defect: expanding the molecular and phenotypic spectrum
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923796/
https://www.ncbi.nlm.nih.gov/pubmed/33672558
http://dx.doi.org/10.3390/genes12020294
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