Analysis of clinical phenotype and genotype in patients with 21-hydroxylase deficiency in Hunan / 中华实用儿科临床杂志

ABSTRACT

Objective:To investigate the clinical characteristic, gene mutations and genotype-phenotype correlation of 21-hydroxylase deficiency (21-OHD) in Hunan.Methods:A total of 48 patients with 21-OHD who were admitted to the Department of Pediatrics, the Second Xiangya Hospital, Central South University from March 2016 to March 2017 were collected.According to the clinical manifestations and biochemical characteristics of the patients, they were divided into salt wasting (SW) and simple virilizing (SV). Sanger sequencing combined with multiplex ligation-dependent probe amplification(MLPA) were used to detect the mutations of CYP21A2 gene.The patients were divided into 3 groups according to their mutations severity severe mutation group, moderate mutation group and unknown mutation group.Then, the correlation between genotype and phenotype was analyzed. Results:(1) Forty-eight 21-OHD patients included 28 SW cases and 20 SV cases, and the first visiting age of SW was younger than that of SV, and the difference was statistically significant ( U=44.5, P<0.05). The SW cases had high incidence rate of adrenal crisis and the SV patients were liable to advanced bone age and precocious puberty.(2) Forty-four patients were detected abnormal gene mutation and the positive rate of genetic diagnosis was 91.7%.Fourteen mutation types including I2G, Del, I173N, R357W, R484fs(c.1451_1452delGGinsC, c.1450dupC), R483fs, G111Vfs*21, Q319X, c.292+ 1G>A, c.377C>G, E6Cluster, p.H393Q and m. 1647C>T, were found in 88 alleles.The most frequent mutations were I2G(36.4%), I173N(20.4%), and Del(22.7%). p.H393Q and m. 1647C>T were 2 novel mutations.I2G (47.3%) and Del (27.3%) were the most frequent mutations in SW cases, and I173N (48.5%) was the most frequent mutation in SV cases.(3) Severe mutation was in 29 patients, including 26 SW, and moderate mutation was in 13 patients, including 12 SW.The percentage of SW in severe mutation group was 89.7% and SV in moderate mutation was 92.3%. Conclusions:I2G, I173N and Del were the frequent mutations of 21-OHD in Hunan, and the total percen-tage was 79.5%.Genotype of 21-OHD has strong correlation with clinical phenotype, which can effectively predict SW by severe mutation and predict SV by moderate mutation.