Genotype And Clinical Phenotype In Classical 21-Hydroxylase Deficiency Patients

Objective To know the characteristic of 21-hydroxylase deficiency patients’ CYP21A2 gene mutation and the relations between the genotype and clinical phenotypes.Subject and Method 132 21-hydroxylase deficiency patients(SW 83 cases, SV 49 cases) who were diagnosed based on clinical manifestation and got CYP21A2 gene tests in Children’s Hospital of Chongqing Medical University from October 2011 to January 2016. Genetic testing method is PCR-ACRS and Sanger sequencing. Genotype was classified into 3 groups according to its severity: severe mutation group, composed of homozygous and compound heterozygous mutation with severe mutation; moderate mutation group, composed of homozygous mutation with I173 N, compound heterozygous mutation with I173 and severe mutation; mild mutation group, composed of homozygous mutation with mild mutation and compound heterozygous mutation with mild and the others.Result 117 patients were detected abnormal gene mutation, 8 patients only had nonsense mutation and 7 patients didn’t test abnormal gene mutation. There are 36 kinds of gene mutations except for nonsense mutations, 0nly 16 kinds of mutations can inquiry from previous literature, whether the other 20 kinds will affect the 21-OH activity are unknown. Positive rate of genetic diagnosis is only 65.2%. There are 54 SW and 7 SV patients in the severe mutation group, 1 SW and 20 SV patients in the moderate mutation group, 4 SV patients in the mild mutation group. The newly diagnosed age of severe mutation group(0.1 years old) was significantly lower than those of moderate and mild mutation groups(3.6 and 3.15 years old). The percentage of SW patients in severe mutation group(88.5%) is higher than the other two groups. Most common gene mutations are I172N(34.7%)、 I2g(21.4%)、 Q318X(6.4%) and R356W(5.7%). I2g(47.6%) is the most common in SW patients, I173N(34.7%) and I2g(21.4%)are the most common in SV patients.Conclusion Genotype of 21-OHD has strong correlation with clinical phenotypes, which can effectively predict the clinical phenotype based on the gene mutation severity, help diagnose, treatment and genetic counseling. most common mutations in our study are I172N(34.7%)、I2g(21.4%)、Q318X(6.4%)and R356W(5.7%), which is similar to the distribution of gene frequency in Shanghai but some different from that in Beijing, Taiwan and Xinjiang. Only use PCR-ACRS and Sanger sequencing to test the mutation and report the base mutation and the amino acid change, the positive rate of genetic diagnosis was low.