Revealing Chronic Granulomatous Disease in a Patient With Williams-Beuren Syndrome Using Whole Exome Sequencing.

Autor:	Ripen AM; Primary Immunodeficiency Unit, Allergy and Immunology Research Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health Malaysia, Selangor, Malaysia., Chiow MY; Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia., Rama Rao PR; Pediatrics Department, Keningau Hospital, Ministry of Health Malaysia, Sabah, Malaysia., Mohamad SB; 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.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2021 Nov 04; Vol. 12, pp. 778133. Date of Electronic Publication: 2021 Nov 04 (Print Publication: 2021).
DOI:	10.3389/fimmu.2021.778133
Abstrakt:	Blended phenotypes exhibited by a patient may present a challenge to the establishment of diagnosis. In this study, we report a seven-year-old Murut girl with unusual features of Williams-Beuren syndrome (WBS), including recurrent infections and skin abscesses. Considering the possibility of a second genetic disorder, a mutation screening for genes associated with inborn errors of immunity (IEI) was conducted using whole exome sequencing (WES). Analysis of copy number variations (CNVs) from the exome data revealed a 1.53Mb heterozygous deletion on chromosome 7q11.23, corresponding to the known WBS. We also identified a biallelic loss of NCF1 , which indicated autosomal recessive chronic granulomatous disease (CGD). Dihydrorhodamine (DHR) flow cytometric assay demonstrated abnormally low neutrophil oxidative burst activity. Coamplification of NCF1 and its pseudogenes identified a GT-deletion (ΔGT) at the start of exon 2 in NCF1 (NM_000265.7: c.75_76delGT: p.Tyr26Hisfs*26). Estimation of NCF1 -to- NCF1 pseudogenes ratio using ΔGT and 20-bp gene scans affirmed nil copies of NCF1 in the patient. While the father had a normal ratio of 2:4, the mother had a ratio of 1:5, implicating the carrier of ΔGT-containing NCF1 . Discovery of a 7q11.23 deletion involving one NCF1 allele and a ΔGT in the second NCF1 allele explained the coexistence of WBS and CGD in our patient. This study highlights the capability of WES to establish a molecular diagnosis for a case with blended phenotypes, enabling the provision of appropriate prophylactic treatment. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Ripen, Chiow, Rama Rao and Mohamad.)
Databáze:	MEDLINE
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