Approach to Molecular Diagnosis of Chronic Granulomatous Disease (CGD): an Experience from a Large Cohort of 90 Indian Patients

Kulkarni, Manasi; Hule, Gouri; Boer, Martin de; Leeuwen, Karin van; Kambli, Priyanka; Aluri, Jahnavi; Gupta, Maya; Dalvi, Aparna; Mhatre, Snehal; Taur, Prasad; Desai, Mukesh; Madkaikar, Manisha

doi:10.1007/s10875-018-0567-y

Cited by 26 publications

(20 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This mainly affects the severity of the clinical progression. However, previous studies have also shown that the amount of residual superoxide activity is dependent on the type of mutation in the affected gene (44, 48, 55). These diagnostic tests do not help to identify the exact genotype (except for the XL-CGD where mother is the carrier of the disease).…”

Section: Chronic Granulomatous Diseases (Cgd)mentioning

confidence: 96%

“…The overlapping clinical manifestations and generic patterns in diagnostic tests sometimes mask the underlying genotype of CGD during an initial diagnosis. Significant differences are observed in age at diagnosis, residual superoxide activity, clinical course, and mean survival age among the CGD subtypes (41, 44, 48, 49).…”

Section: Chronic Granulomatous Diseases (Cgd)mentioning

confidence: 99%

“…Overall, X-linked (XL)-CGD (due to mutations in CYBB gene) is the most prevalent (65%) type of CGD (42, 43). However, a higher rate of autosomal recessive (AR)-CGD (due to mutations in CYBA, NCF1, NCF2, NCF4 genes ) is reported in the regions where consanguineous marriage is more common (44, 45). It is characterized by the inability of phagocytes to form reactive oxygen species (ROS) upon interaction with bacterial or fungal pathogens (46).…”

Section: Chronic Granulomatous Diseases (Cgd)mentioning

confidence: 99%

“…Particularly, NCF1 gene has two pseudogenes (>99% homology), which are difficult to analyze by either the Sanger or NGS method, and require a simple Gene Scan analysis to identify the most common Del GT mutation (at the beginning of exon 2) (66). In such cases, flow cytometric evaluation could play an important role in making the choice of appropriate method for further molecular characterization of CGD patients (44, 67).…”

Section: Chronic Granulomatous Diseases (Cgd)mentioning

confidence: 99%

“…Among them, a genotype could not be identified using flow cytometric evaluation in two patients. In a country like India with limited resources, the predominance of AR-CGD type, and a high frequency of consanguineous marriages, the flow cytometric classification of CGD patients remains a vital tool in the early diagnosis and guide for molecular characterization (by suggesting appropriate method) (44, 68) (Figure 9).…”

Section: Chronic Granulomatous Diseases (Cgd)mentioning

confidence: 99%

See 4 more Smart Citations

Application of Flow Cytometry in Primary Immunodeficiencies: Experience From India

et al. 2019

Self Cite

View full text Add to dashboard Cite

Primary immunodeficiency diseases (PID) are a clinically and immunologically heterogeneous group of disorders of immune system. Diagnosis of these disorders is often challenging and requires identification of underlying genetic defects, complemented by a comprehensive evaluation of immune system. Flow cytometry, with its advances in the last few decades, has emerged as an indispensable tool for enumeration as well as characterization of immune cells. Flow cytometric evaluation of the immune system not only provides clues to underlying genetic defects in certain PIDs and helps in functional validation of novel genetic defects, but is also useful in monitoring immune responses following specific therapies. India has witnessed significant progress in the field of flow cytometry as well as PID over last one decade. Currently, there are seven Federation of Primary Immunodeficiency Diseases (FPID) recognized centers across India, including two Indian Council of Medical research (ICMR) funded centers of excellence for diagnosis, and management of PIDs. These centers offer comprehensive care for PIDs including flow cytometry based evaluation. The key question which always remains is how one selects from the wide array of flow cytometry based tests available, and whether all these tests should be performed before or after the identification of genetic defects. This becomes crucial, especially when resources are limited and patients have to pay for the investigations. In this review, we will share some of our experiences based on evaluation of a large cohort of hemophagocytic lymphohistiocytosis, severe combined immunodeficiency, and chronic granulomatous disease, and the lessons learned for optimum use of this powerful technology for diagnosis of these disorders.

show abstract

Section: Chronic Granulomatous Diseases (Cgd)mentioning

confidence: 96%

Section: Chronic Granulomatous Diseases (Cgd)mentioning

confidence: 99%

Section: Chronic Granulomatous Diseases (Cgd)mentioning

confidence: 99%

Section: Chronic Granulomatous Diseases (Cgd)mentioning

confidence: 99%

Section: Chronic Granulomatous Diseases (Cgd)mentioning

confidence: 99%

See 3 more Smart Citations

Application of Flow Cytometry in Primary Immunodeficiencies: Experience From India

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

Profile of 208 patients with inborn errors of immunity at a tertiary care center in South India

Bhattad,

Mohite,

Singh

et al. 2023

Clin Exp Med

View full text Add to dashboard Cite

Primary immune de ciencies better known as Inborn Errors of Immunity (IEI) are a heterogeneous group of disorders that predispose affected individuals to infections, allergy, autoimmunity, autoin ammation, and malignancies.. Inborn Errors of Immunity are increasingly being recognized in the Indian subcontinent. Two hundred and eight patients diagnosed with an IEI during February 2017 to November 2021 at a tertiary care centre in South India were included in the study. The clinical features, laboratory ndings including microbiologic and genetic data, treatment & outcome details were analyzed. The diagnosis of IEI was con rmed in a total of 208 patients (198 kindreds) based on relevant immunological tests and/or genetic tests. The male to female ratio was 1.8:1. The most common IEI in our cohort was SCID (17.7%) followed by CGD (12.9%) and CVID (9.1%). We also had a signi cant proportion of patients with DOCK8 de ciency (7.2%), LAD (6.2%), and six patients (2.8%) with autoin ammatory diseases. Autoimmunity was noted in forty-six (22%) patients during the course of their illness. Molecular testing was performed in 152 patients by exome sequencing on NGS platform and a genetic variant was reported in 132 cases. Twenty-nine children underwent 34 HSCT, and 135 patients remain on supportive therapy such as immunoglobulin replacement and/or antimicrobial prophylaxis. Fifty-nine (28.3%) patients died during the study period and infections were the predominant cause of mortality. Seven families underwent prenatal testing in the subsequent pregnancy. We describe the pro le of 208 patients with IEI and to the best of our knowledge, this represents the largest data on IEI from the Indian subcontinent reported so far.Patient details such as the age at onset of symptoms, clinical presentation, age at diagnosis, family history, laboratory ndings including microbiologic data, treatment & outcome details were recorded. Clinical details included both infectious and noninfectious manifestations (allergy, autoimmunity, malignancy, etc) at presentation and in the past. A family history with a focus on consanguineous parentage, sibling death if any, and details of the affected family members were obtained. Family history was considered positive in case of an affected family member. Treatment details including antimicrobial prophylaxis, intravenous

show abstract

NAPDH Oxidase-Specific Flow Cytometry Allows for Rapid Genetic Triage and Classification of Novel Variants in Chronic Granulomatous Disease

et al. 2019

View full text Add to dashboard Cite

Approach to Molecular Diagnosis of Chronic Granulomatous Disease (CGD): an Experience from a Large Cohort of 90 Indian Patients

Cited by 26 publications

References 39 publications

Application of Flow Cytometry in Primary Immunodeficiencies: Experience From India

Application of Flow Cytometry in Primary Immunodeficiencies: Experience From India

Profile of 208 patients with inborn errors of immunity at a tertiary care center in South India

NAPDH Oxidase-Specific Flow Cytometry Allows for Rapid Genetic Triage and Classification of Novel Variants in Chronic Granulomatous Disease

Contact Info

Product

Resources

About