A novel chimeric CYP11B2/CYP11B1 combined with a new p.L340P CYP11B1 mutation in a patient with 11OHD: case report

BACKGROUND: 11β-Hydroxylase deficiency (11OHD) is a common form of congenital adrenal hyperplasia that has been shown to result from inactivating CYP11B1 mutations, and pathogenic CYP11B2/CYP11B1 chimeras contribute to a minority of cases. Heterozygote cases (chimeras combined with missense mutation) are very rare, and genetic analysis of these cases is difficult. CASE PRESENTATION: We describe an 11OHD patient presenting with precocious pseudopuberty and hypokalemia hypertension who harbored a chimeric CYP11B2/CYP11B1 with a novel breakage point located at g.9559–9742 of CYP11B2. Interestingly, the other allele exhibited a new mutation, p.L340P, in CYP11B1. Bioinformatics and molecular dynamics simulation indicated that p.L340P decreased the stability and changed the surface configuration of 11β-hydroxylase, indicating a disease-causing mutation. Further pedigree study, PCR and next-generation sequencing indicated that the proband carried both the chimera and p.L340P, and coexistence of the two increased the severity of 11OHD in this family. After treatment with combined medications, blood pressure and clinical parameters improved. CONCLUSIONS: Our results suggest that chimera screening and CYP11B1 mutation screening should be simultaneously conducted, and pedigree study is necessary. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12902-018-0249-z) contains supplementary material, which is available to authorized users.