Publications by authors named "Hamidah Ghani"

6 Publications

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A single-center pilot study in Malaysia on the clinical utility of whole-exome sequencing for inborn errors of immunity.

Clin Exp Immunol 2021 Jun 1. Epub 2021 Jun 1.

Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.

Primary immunodeficiency diseases refer to inborn errors of immunity (IEI) that affect the normal development and function of the immune system. The phenotypical and genetic heterogeneity of IEI have made their diagnosis challenging. Hence, whole-exome sequencing (WES) was employed in this pilot study to identify the genetic etiology of 30 pediatric patients clinically diagnosed with IEI. The potential causative variants identified by WES were validated using Sanger sequencing. Genetic diagnosis was attained in 46.7% (14 of 30) of the patients and categorized into autoinflammatory disorders (n = 3), diseases of immune dysregulation (n = 3), defects in intrinsic and innate immunity (n = 3), predominantly antibody deficiencies (n = 2), combined immunodeficiencies with associated and syndromic features (n = 2) and immunodeficiencies affecting cellular and humoral immunity (n = 1). Of the 15 genetic variants identified, two were novel variants. Genetic findings differed from the provisional clinical diagnoses in seven cases (50.0%). This study showed that WES enhances the capacity to diagnose IEI, allowing more patients to receive appropriate therapy and disease management.
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http://dx.doi.org/10.1111/cei.13626DOI Listing
June 2021

Whole exome sequencing identifies compound heterozygous variants of gene in monozygotic twin patients with common variable immunodeficiency.

SAGE Open Med 2020 22;8:2050312120922652. Epub 2020 May 22.

Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.

Objectives: A pair of female Malay monozygotic twins who presented with recurrent upper respiratory tract infections, hepatosplenomegaly, bronchiectasis and bicytopenia were recruited in this study. Both patients were suspected with primary immunodeficiency diseases. However, the definite diagnosis was not clear due to complex disease phenotypes. The objective of this study was to identify the causative gene mutation in these patients.

Methods: Lymphocyte subset enumeration test and whole exome sequencing were performed.

Results: We identified a compound heterozygous mutation (c.1916G>A and c.2012G>A) in both patients. These variants were then confirmed using Sanger sequencing.

Conclusion: Whole exome sequencing analysis of the monozygotic twins revealed compound heterozygous missense mutations in .
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http://dx.doi.org/10.1177/2050312120922652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7249565PMC
May 2020

A novel de novo NLRC4 mutation reinforces the likely pathogenicity of specific LRR domain mutation.

Clin Immunol 2020 02 20;211:108328. Epub 2019 Dec 20.

Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia; Centre of Research in Systems Biology, Structural Bioinformatics and Human Digital Imaging (CRYSTAL), University of Malaya, Kuala Lumpur, Malaysia. Electronic address:

Autoinflammatory disorders are characterized by dysregulated innate immune response, resulting in recurrent uncontrolled systemic inflammation and fever. Gain-of-function mutations in NLRC4 have been described to cause a range of autoinflammatory disorders. We report a twelve-year-old Malay girl with recurrent fever, skin erythema, and inflammatory arthritis. Whole exome sequencing and subsequent bidirectional Sanger sequencing identified a heterozygous missense mutation in NLRC4 (NM_001199138: c.1970A > T). This variant was predicted to be damaging in silico, was absent in public and local databases and occurred in a highly conserved residue in the leucine-rich repeat (LRR) domain. Cytokine analysis showed extremely high serum IL-18 and IL-18/CXCL9 ratio, consistent with other NLRC4-MAS patients. In summary, we identified the first patient with a novel de novo heterozygous NLRC4 gene mutation contributing to autoinflammatory disease in Malaysia. Our findings reinforce the likely pathogenicity of specific LRR domain mutations in NLRC4 and expand the clinical spectrum of NLRC4 mutations.
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http://dx.doi.org/10.1016/j.clim.2019.108328DOI Listing
February 2020

Probing the interaction of 2,4-dichlorophenoxyacetic acid with human serum albumin as studied by experimental and computational approaches.

Spectrochim Acta A Mol Biomol Spectrosc 2019 Jan 19;207:284-293. Epub 2018 Sep 19.

Bioinformatics Programme, Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia; Centre of Research for Computational Sciences and Informatics for Biology, Bioindustry, Environment, Agriculture and Healthcare, University of Malaya, Kuala Lumpur, Malaysia.

To characterize the binding of a widely used herbicide, 2,4-dichlorophenoxyacetic acid (2,4-D) to the major transporter in human circulation, human serum albumin (HSA), multi-spectroscopic approaches such as fluorescence, absorption and circular dichroism along with computational methods were employed. Analysis of the fluorescence and absorption spectroscopic data confirmed the 2,4-D-HSA complex formation. A static quenching mechanism was evident from the inverse temperature dependence of the K values. The complex was stabilized by a weak binding affinity (K = 5.08 × 10 M at 298 K). Quantitative analysis of thermodynamic data revealed participation of hydrophobic and van der Waals interactions as well as hydrogen bonds in the binding process. Circular dichroism and three-dimensional fluorescence spectral results showed structural (secondary and tertiary) changes in HSA as well as microenvironmental perturbation around protein fluorophores (Trp and Tyr residues) upon 2,4-D binding. Addition of 2,4-D to HSA was found to improve protein's thermal stability. Competitive displacement results as well as computational analyses suggested preferred location of the 2,4-D binding site as Sudlow's site I (subdomain IIA) in HSA.
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http://dx.doi.org/10.1016/j.saa.2018.09.033DOI Listing
January 2019

Biophysical and computational characterization of vandetanib-lysozyme interaction.

Spectrochim Acta A Mol Biomol Spectrosc 2018 Jan 18;189:485-494. Epub 2017 Aug 18.

Biomolecular Research Group, Biochemistry Programme, Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia; Centre of Research for Computational Sciences and Informatics for Biology, Bioindustry, Environment, Agriculture and Healthcare, University of Malaya, Kuala Lumpur, Malaysia. Electronic address:

Interaction of an anticancer drug, vandetanib (VDB) with a ligand transporter, lysozyme (LYZ) was explored using multispectroscopic techniques, such as fluorescence, absorption and circular dichroism along with computational analysis. Fluorescence data and absorption results confirmed VDB-LYZ complexation. VDB-induced quenching was characterized as static quenching based on inverse correlation of K with temperature as well as k values. The complex was characterized by the weak binding constant (K=4.96-3.14×10M). Thermodynamic data (ΔS=+12.82JmolK; ΔH=-16.73kJmol) of VDB-LYZ interaction revealed participation of hydrophobic and van der Waals forces along with hydrogen bonds in VDB-LYZ complexation. Microenvironmental perturbations around tryptophan and tyrosine residues as well as secondary and tertiary structural alterations in LYZ upon addition of VDB were evident from the 3-D fluorescence, far- and near-UV CD spectral analyses, respectively. Interestingly, addition of VDB to LYZ significantly increased protein's thermostability. Molecular docking results suggested the location of VDB binding site near the LYZ active site while molecular dynamics simulation results suggested stability of VDB-LYZ complex. Presence of Mg, Ba and Zn was found to interfere with VDB-LYZ interaction.
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http://dx.doi.org/10.1016/j.saa.2017.08.051DOI Listing
January 2018

Interactive association between RhoA transcriptional signaling inhibitor, CCG1423 and human serum albumin: Biophysical and in silico studies.

J Biomol Struct Dyn 2018 Aug 18;36(10):2495-2507. Epub 2017 Aug 18.

a Biomolecular Research Group, Biochemistry Programme, Institute of Biological Sciences, Faculty of Science , University of Malaya , Kuala Lumpur , Malaysia.

Multiple spectroscopic techniques, such as fluorescence, absorption, and circular dichroism along with in silico studies were used to characterize the binding of a potent inhibitor molecule, CCG1423 to the major transport protein, human serum albumin (HSA). Fluorescence and absorption spectroscopic results confirmed CCG1423-HSA complex formation. A strong binding affinity stabilized the CCG1423-HSA complex, as evident from the values of the binding constant (K = 1.35 × 10-5.43 × 10 M). The K values for CCG1423-HSA system were inversely correlated with temperature, suggesting the involvement of static quenching mechanism. Thermodynamic data anticipated that CCG1423-HSA complexation was mainly driven by hydrophobic and van der Waals forces as well as hydrogen bonds. In silico analysis also supported these results. Three-dimensional fluorescence and circular dichroism spectral analysis suggested microenvironmental perturbations around protein fluorophores and structural (secondary and tertiary) changes in the protein upon CCG1423 binding. CCG1423 binding to HSA also showed some protection against thermal denaturation. Site-specific marker-induced displacement results revealed CCG1423 binding to Sudlow's site I of HSA, which was also confirmed by the computational results. A few common ions were also found to interfere with the CCG1423-HSA interaction.
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http://dx.doi.org/10.1080/07391102.2017.1360207DOI Listing
August 2018
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