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.
Carotenoids are isoprenoid pigments synthesized exclusively by plants and microorganisms and play critical roles in light harvesting, photoprotection, attracting pollinators and phytohormone production. In recent years, carotenoids have been used for their health benefits due to their high antioxidant activity and are extensively utilized in food, pharmaceutical, and nutraceutical industries. Regulation of carotenoid biosynthesis occurs throughout the life cycle of plants, with vibrant changes in composition based on developmental needs and responses to external environmental stimuli. With advancements in metabolic engineering techniques, there has been tremendous progress in the production of industrially valuable secondary metabolites such as carotenoids. Application of metabolic engineering and synthetic biology has become essential for the successful and improved production of carotenoids. Synthetic biology is an emerging discipline; metabolic engineering approaches may provide insights into novel ideas for biosynthetic pathways. In this review, we discuss the current knowledge on carotenoid biosynthetic pathways and genetic engineering of carotenoids to improve their nutritional value. In addition, we investigated synthetic biological approaches for the production of carotenoids. Theoretical biology approaches that may aid in understanding the biological sciences are discussed in this review. A combination of theoretical knowledge and experimental strategies may improve the production of industrially relevant secondary metabolites.