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

• Main Authors: Abdulaziz Asiri, Deemah Alwadaani, Muhammad Umair, Kheloud M. Alhamoudi, Mohammed H. Almuhanna, Abdul Nasir, Bahauddeen M. Alrfaei, Abeer Al Tuwaijri, Tlili Barhoumi, Yusra Alyafee, Bader Almuzzaini, Mohammed Aldrees, Mariam Ballow, Latifah Alayyar, Abdulkareem Al Abdulrahman, Yazeid Alhaidan, Nahlah Al Ghasham, Sulaiman Al-Ajaji, Mohammad Alsalamah, Wafa Al Suwairi, Majid Alfadhel
• Format: Article
• Language: English
• Published: MDPI AG 2021-02-01
• Series: Genes
• Subjects: CDC42; a de novo missense variant; poor wound healing; pancytopenia; recurrent infections
• Online Access: https://www.mdpi.com/2073-4425/12/2/294

<b>: </b>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 <i>CDC42</i> 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 <i>CDC42</i> 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,<b> </b>we report a candidate disease-causing variant, which requires further confirmation for the etiology of <i>CDC42</i> pathogenesis. This represents the first case from the Saudi population. The current study adds to the spectrum of mutations in the <i>CDC42</i> 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 <i>CDC42</i> gene associated with aberrant cell migration and immune response.