Clinical And Genetic Analysis Of 8 Patients With 11?-hydroxylase Deficiency

Objective:To explore the clinical phenotypic characteristics of11?-hydroxylase deficiency and the correlation between clinical phenotype and genotype by analyzing the clinical manifestations and genetic basis of8 patients with 11?-hydroxylase deficiency.Methods:Summarizing and analyzing the clinical manifestations,hormone levels,imaging examinations,gene mutations and therapeutic effect of 8 patients?6 females and 2 males?with 11?-hydroxylase deficiency diagnosed in the Children's Hospital of Chongqing Medical University from 2013 to 2019.Results:Six girls were found different degrees of virilization in external genitalia,and two boys were found precocious puberty.Thre e patients were found to have hypertension.The determination of hor mone levels and ACTH stimulation test were consistent with the pat hophysiological mechanism of 11?-OHD.we conducted gene examinati on in 8 patients,and found 4 cases of chimera of CYP11B2/CYP11B1 gene,2 cases of complex heterozygosity,and 2 cases of intron mutation,including 6 novel mutations of CYP11B1 gene: c.800-3t>G,c.61delG?p.A21 Hfs *30?,c.595+5G>A,c.239+1G>c,c.1145T>C?p.L382P?,c.823₈26delTATC?p.Y275 Rfs *20?.Conclusion:The main manifestations of classical 11?-OHD are varying degrees of virilization in girls' external genitalia when they were born and precocious puberty in both boys and girls,and some patients have hyporenin hypertension and hypokalemia.And the clinical manifestations of CYP11B2/CYP11B1 chimera are consistent with that of classical11?-OHD.Laboratory examination shows that 17-OHP and DHEA increased slightly,AND increased significantly,and renin activity decreased.However,increased renin activity is also observed in some infants.During the treatment of 11?-OHD,the main reference indexes of doses are AND,17-OHP and renin.It is necessary to keep AND and17-OHP within the normal range of children of the same age and gender,and renin should be maintained at the normal high limit or slightly above the normal high limit in order to delay the progression of bone age.the study enrichs the gene mutation spectrum of 11?-hydroxylase deficiency and provides help for genetic counseling and prenatal diagnosis.The clinical manifestations of 11beta-hydroxylase deficiency are diverse and the mutation types are numerous,so the screening of CYP11B1 mutation types and chimera of CYP11B2/CYP11B1 screening should be conducted simultaneously in the gene detection.