{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T06:14:04Z","timestamp":1790403244274,"version":"4.1.0"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,11,4]],"date-time":"2021-11-04T00:00:00Z","timestamp":1635984000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013885","name":"Kementerian Kesihatan Malaysia","doi-asserted-by":"publisher","award":["MOH Research Grant (MRG)"],"award-info":[{"award-number":["MOH Research Grant (MRG)"]}],"id":[{"id":"10.13039\/501100013885","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>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 <jats:italic>NCF1<\/jats:italic>, which indicated autosomal recessive chronic granulomatous disease (CGD). Dihydrorhodamine (DHR) flow cytometric assay demonstrated abnormally low neutrophil oxidative burst activity. Coamplification of <jats:italic>NCF1<\/jats:italic> and its pseudogenes identified a GT-deletion (\u0394GT) at the start of exon 2 in <jats:italic>NCF1<\/jats:italic> (NM_000265.7: c.75_76delGT: p.Tyr26Hisfs*26). Estimation of <jats:italic>NCF1<\/jats:italic>-to-<jats:italic>NCF1<\/jats:italic> pseudogenes ratio using \u0394GT and 20-bp gene scans affirmed nil copies of <jats:italic>NCF1<\/jats:italic> 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 \u0394GT-containing <jats:italic>NCF1<\/jats:italic>. Discovery of a 7q11.23 deletion involving one <jats:italic>NCF1<\/jats:italic> allele and a \u0394GT in the second <jats:italic>NCF1<\/jats:italic> 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.<\/jats:p>","DOI":"10.3389\/fimmu.2021.778133","type":"journal-article","created":{"date-parts":[[2021,11,4]],"date-time":"2021-11-04T05:30:38Z","timestamp":1636003838000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Revealing Chronic Granulomatous Disease in a Patient With Williams-Beuren Syndrome Using Whole Exome Sequencing"],"prefix":"10.3389","volume":"12","author":[{"given":"Adiratna Mat","family":"Ripen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei Yee","family":"Chiow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prakash Rao","family":"Rama 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