摘要：

目的 分析兒童原發(fā)性腎上腺皮質(zhì)功能減退患者的臨床特征及其DAX1、SF1基因突變的發(fā)生率，探討導(dǎo)致該病可能的分子機(jī)制。方法 選擇原發(fā)性腎上腺皮質(zhì)功能減退的男性患兒25例，觀察患兒的臨床特征并行輔助檢查。抽提外周血基因組DNA，對DAX1基因2個(gè)外顯子（外顯子1和2）的PCR擴(kuò)增產(chǎn)物進(jìn)行測序分析；無突變者行SF1基因(外顯子2~7)突變篩查。結(jié)果 患兒均有不同程度的皮膚色素沉著、乏力、惡心、嘔吐及脫水等表現(xiàn)；18例曾出現(xiàn)腎上腺危象；8例有明確家族史。15例達(dá)到青春發(fā)育年齡的患兒中，8例（53.3%）伴性發(fā)育不良。DAX1基因檢測共發(fā)現(xiàn)8種突變，包括1種錯(cuò)義、6種移碼和1種無義突變；其中6種（c.291delC、c.332-333delCT、p.E137X、c.605delG、c.731delG和c.838delG）為新發(fā)現(xiàn)突變，余為已報(bào)道過的突變：2例為p.L262P（表兄弟），1例為c.652-653delCA；未發(fā)現(xiàn)SF1基因突變存在。DAX1基因突變率為40%（10/25），伴性發(fā)育不良患兒突變率為62.5%（5/8），有明確家族史患兒DAX1基因突變率為100%（8/8）；DAX1基因突變患兒的發(fā)病年齡不同，臨床表現(xiàn)呈多樣性。結(jié)論 DAX1基因突變是導(dǎo)致兒童原發(fā)性腎上腺皮質(zhì)功能減退的常見分子病因，而SF1突變較罕見；DAX1基因突變臨床表現(xiàn)不一，尚未發(fā)現(xiàn)基因突變類型與臨床表型之間存在明確關(guān)系。

關(guān)鍵詞: 原發(fā)性腎上腺皮質(zhì)功能減退, DAX1基因, SF1基因, 突變, 兒童

Abstract:

Objective To observe the clinical manifestations in children with primary adrenal insufficiency, investigate the prevalences of DAX1 and SF1 gene mutations, and explore the possible mechanism of the disease. Methods Twentyfive boys with primary adrenal insufficiency were enrolled, the clinical characteristics were observed, and assistant examinations were performed. Genome DNA was extracted from peripheral blood, exon 1 and exon 2 of DAX1 gene were amplified by PCR for sequencing, and mutation screening of SF1 gene (exon 2-7) was conducted. Results There were symptoms of hyperpigmentation in skin, fatigue and weakness, nausea, vomiting and dehydration in all patients. Adrenal crisis occurred in 18 patients, and 8 patients had definite family history. Eight (53.3%) of the 15 adolescents had impaired sex development. Analysis of DAX1 gene identified 8 mutations (6 frameshift mutations,1 missense mutation and 1 nonsense mutation), six of which were novel (c.291delC, c.332-333delCT, p.E137X, c.605delG, c.731delG and c.838delG), and the other two (p.L262P in two male cousins and c.652-653delCA in 1 patient) had been reported. No SF1 gene mutation was identified. DAX1 gene mutations were found in 40% (10/25) of patients, in 62.5% (5/8) of those with impaired sex development, and in 100%(8/8) of those with family history. There were various clinical presentations and ages in patients with DAX1 gene mutations. Conclusion DAX1 gene mutations may be a frequent cause of primary adrenal insufficiency in children, while mutation in SF1 seldomly occurs. There are various clinical manifestations for gene mutations, and there may be no definite relationship between gene mutations and clinical manifestations.

Key words: primary adrenal insufficiency, DAX1 gene, SF1 gene, mutation, children

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網(wǎng)址: 兒童原發(fā)性腎上腺皮質(zhì)功能減退的臨床特征和基因突變研究 http://www.u1s5d6.cn/newsview956103.html