Case Report: Identification of Polygenic Mutations by Exome Sequencing.

Area of Science:

• Human Genetics
• Genomics
• Molecular Biology

Background:

• Rare genetic variation discovery is challenging.
• Exome sequencing (ES) is a powerful tool for identifying genetic causes of rare diseases.

Observation:

• A 1-year-old boy presented with complex, seemingly unrelated symptoms including metabolic acidosis, hypokalemia, G6PD deficiency, micropenis, and growth retardation.
• Exome sequencing was performed on the patient and his parents due to the complex clinical presentation.

Findings:

• Three significant locus mutations were identified in the proband across three genes: SLC4A1, FGFR1, and G6PD.
• A de novo missense mutation (c.1766G>T, p.R589L) was found in exon 14 of the SLC4A1 gene.
• Another de novo missense mutation (c.1028A>G, p.H343R) was identified in exon 9 of the FGFR1 gene.

Implications:

• These findings underscore the diagnostic utility of exome sequencing for rare genetic disorders with complex phenotypes.
• Identification of de novo mutations in SLC4A1 and FGFR1 provides insights into the genetic basis of the patient's condition.
• This case demonstrates the value of advanced genetic sequencing in unraveling the etiology of undiagnosed diseases.