Publications by authors named "Mohd Farid Baharin"

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

Atypical Presentation of Severe Fungal Necrotizing Fasciitis in a Patient with X-Linked Agammaglobulinemia.

J Clin Immunol 2021 Aug 13;41(6):1178-1186. Epub 2021 Mar 13.

Primary Immunodeficiency Unit, Allergy and Immunology Research Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health, Selangor, Malaysia.

X-linked agammaglobulinemia is a rare primary immunodeficiency due to a BTK mutation. The patients are characteristically deficient in peripheral B cells and serum immunoglobulins. While they are susceptible to infections caused by bacteria, enteroviruses, and parasites, fungal infections are uncommon in XLA patients. Here, we report a boy of Malay ethnicity who suffered from recurrent upper respiratory tract infections and severe progressive necrotizing fasciitis caused by Saksenaea erythrospora. Immunological tests showed a B cell deficiency and hypogammaglobulinemia. Whole-exome sequencing identified a dinucleotide deletion (c.1580_1581del) in BTK, confirmed by Sanger sequencing and predicted to be disease causing by in silico functional prediction tools (Varsome and MutationTaster2) but was absent in the gnomAD database. This mutation resulted in a frameshift and premature termination (p.C527fs), which disrupted the protein structure. The mother was heterozygous at the mutation site, confirming her carrier status. Flow cytometric analysis of monocyte BTK expression showed it to be absent in the patient and bimodal in the mother. This study describes a novel BTK mutation in a defined hotspot and an atypical fungal phenotype in XLA. Further studies are required to understand the pathogenesis of fungal infection in XLA.
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http://dx.doi.org/10.1007/s10875-021-01017-3DOI Listing
August 2021

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

HLA-A, -B, -C, -DRB1 and -DQB1 alleles and haplotypes in 951 Southeast Asia Malays from Peninsular Malaysia.

Hum Immunol 2016 Oct 29;77(10):818-819. Epub 2016 Jun 29.

Allergy and Immunology Research Center, Institute for Medical Research, Kuala Lumpur, Malaysia; Rheumatology Unit, Department of Medicine, CMM L8:O4, Karolinska University Hospital and Karolinska Institutet, 17176 Stockholm, Sweden. Electronic address:

A total of 951 Southeast Asia Malays from Peninsular Malaysia were genotyped for HLA-A, -B, -C -DRB1, and -DQB1 loci using polymerase chain reaction sequence-specific oligonucleotide probe hybridization methods. In this report, there were significant deviation from Hardy-Weinberg proportions for the HLA-A (p<0.0001), -B (p<0.0001), -DRB1 (p<0.0001) and -DQB1 (p<0.01) loci. Minor deviations from HWEP were detected for HLA-C (p=0.01). This genotype data was available in Allele Frequencies Network Database (AFND) Gonzalez-Galarza et al. (2015).
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http://dx.doi.org/10.1016/j.humimm.2016.06.022DOI Listing
October 2016

A rare case of Wiskott-Aldrich Syndrome with normal platelet size: a case report.

J Med Case Rep 2016 Jun 29;10(1):188. Epub 2016 Jun 29.

Department of Pediatrics, Hospital Pulau Pinang, Jalan Residensi, 10450, George Town, Pulau Pinang, Malaysia.

Background: Wiskott-Aldrich syndrome is a rare X-linked disorder characterized by microthrombocytopenia, eczema, and recurrent infections. It is caused by mutations of the WAS gene. Microthrombocytopenia has been regarded as the key criteria in diagnosing this rare condition. However, in this case report, we describe a case of Wiskott-Aldrich syndrome with normal platelet size.

Case Presentation: We report the case of a 9-month-old Malay boy who presented with persistent thrombocytopenia from birth. Serial blood investigations at birth showed he had normal platelet size. His family history revealed two early neonatal deaths in maternal uncles. Spontaneous bleeding was only seen at the age of 3 months. He was initially treated for immune thrombocytopenic purpura and was started on intravenously administered immunoglobulin. His clinical deterioration and poor response to the immunoglobulin raised suspicion for a different underlying pathology. Molecular analysis of the WAS gene revealed a missense mutation in exon 10. His parents refused further interventions and defaulted on subsequent follow-up appointments.

Conclusions: A diagnosis of Wiskott-Aldrich syndrome should be considered in any male infant who presents with early onset thrombocytopenia despite an absence of small platelet size, a characteristic feature of Wiskott-Aldrich syndrome.
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http://dx.doi.org/10.1186/s13256-016-0944-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4928304PMC
June 2016

Molecular characterization of two Malaysian patients with Wiskott-Aldrich syndrome.

Malays J Pathol 2015 Aug;37(2):153-8

Institute for Medical Research, Allergy and Immunology Research Centre, Jalan Pahang, 50588 Kuala Lumpur, Malaysia.

The Wiskott-Aldrich Syndrome (WAS) is an X-linked immunodeficiency condition characterized by microthrombocytopenia, eczema and recurrent infections. It is caused by mutations in the Wiskott-Aldrich Syndrome protein (WASP) gene. We investigated two Malay boys who presented with congenital thrombocytopenia, eczema and recurrent infections. Here we report two cases of WASP mutation in Malaysia from two unrelated families. One had a novel missense mutation in exon 1 while the other had a nonsense mutation in exon 2. Both patients succumbed to diseaserelated complications. A differential diagnosis of WAS should be considered in any male child who present with early onset thrombocytopenia, especially when this is associated with eczema and recurrent infections.
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August 2015
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