Preliminary study on chronic granulomatous disease in Sri Lanka View Full Text


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Article Info

DATE

2018-09-17

AUTHORS

Shalinda Jude Arjuna Fernando, Noorul Mifra Faiz, Shiroma Mangaika Handunnetti, Aruna Dharshan De Silva, Wasala Mudiyanselage Dhanushka Kumari Dasanayake, Geethani Devika Wickramasinghe, Rathnayake Mudiyanselage Chandima Hasanthi Karunatilake, Nilhan Rajiva de Silva

ABSTRACT

Background: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency of the phagocytic cells, which results in absent or diminished levels of microbicidal reactive oxygen species. The disease occurs due to germline mutations in the genes encoding the five subunits of NADPH oxidase complex. The present study is a pilot study to understand the clinical and genetic aspects of CGD in Sri Lanka. Methods: Clinical records of thirteen CGD patients were analysed and compared with similar studies performed in different countries and regions to identify patterns in demographics, clinical manifestations and infectious agents. Genomic DNA and cDNA were analysed in eight patients to identify mutations in CYBB and NCF1 genes, thereby to ascertain the potential X-linked and autosomal recessive (AR) CGD patients. Results: The onset of symptoms in the patient cohort was very early (mean 4.6 months) compared to 20 months in India and 23.9 months in Latin America. Similarly, the age at diagnosis was lower (mean 1.6 years after birth) compared to other studies; 4.5 years in India and 6.1 years in Europe. Pulmonary manifestations were the most common (85%), followed by skin/subcutaneous infections (77%) and lymphadenopathy (62%). The death rate of local patients (38%) was higher than other countries (India 35%, Europe 20%). Majority (77%) were treated for tuberculosis at some point in life. Genetic analysis confirmed six out of eight patients as X-linked CGD cases with mutations in CYBB gene. A novel splice site mutation was identified in P-07 at position c.141+6 which resulted in the deletion of entire exon 2. Two siblings (P-05 and P-06) from consanguineous parents, were identified with AR-CGD based on the homozygous GT deletion mutation in NCF1 gene. Conclusions: The clinical presentation, manifestations and genetic subtypes in the local cohort, appear to be comparable with global trends. Mycobacterial infections should be investigated and treated with more prominence. Effective treatment options are required to control the high mortality rate. More... »

PAGES

37

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http://scigraph.springernature.com/pub.10.1186/s13223-018-0264-7

DOI

http://dx.doi.org/10.1186/s13223-018-0264-7

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https://app.dimensions.ai/details/publication/pub.1104022515

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30237823


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