21-羟化酶缺陷症的临床与基因诊断研究

【作者】 宋文英；

【导师】 陆召麟； 孙念怙； 黄尚志；

【作者基本信息】 中国协和医科大学 ， 内分泌学， 1998， 博士

【摘要】 先天性肾上腺皮质增生症(congenital adrenal hyperplasia，CAH)是一组常染色体隐性遗传性疾病。21-羟化酶缺陷症(21-hydroxylase deficiency，21-OHD)是CAH中最常见的一种，约占所有CAH病例的90％以上。21-OHD通常分为三种临床类型，即失盐型、单纯男性化型和非经典型，其中失盐型和单纯男性化型又合称为经典型。据文献报道，经典型21-OHD的发病率为1／14，554活产，相应的杂合子发生率为1／61，基因频率为0.0082，其中失盐型与单纯男性化型的比例为3.3：1。而非经典型21-OHD的发病率比经典型高得多，并且有明显的种族差异，是人类最常见的常染色体隐性遗传性疾病之一。 迄今为止，国内尚未见到一定规模的21-OHD的临床或基础研究报道，关于中国人中21-OHD各临床类型的发病情况、该病的临床、生化和遗传学特点，以及药物干预所带来的益处和治疗中存在的问题等等许多方面的问题都有待于我们去进一步观察。本研究的目的在于，对21-OHD患者的发病、临床和治疗特点进行较全面的分析总结，并对引起21-OHD的基因缺失和八种常见点突变进行研究，初步了解中国人中21-OHD的基因突变情况，建立起临床可行的21-OHD的基因诊断方法，并将基因诊断的方法初步应用于临床诊断和产前诊断，以及对21-OHD基因型与临床表现型之间的关系、在临床上诊断为特发性多毛的妇女中是否有被漏诊的非经典型21-OHD等进行初步探讨。 本研究对我院1964年10月—1993年9月的所有21—OHD病例进行回顾性分析，并从1993年9月起对部分患者和新病人进行前瞻性观察至1997年11月，共分析病例148例。观察的指标包括，患者的性别，家族史，初诊年龄，初诊时的临床表现包括失更多还原

【Abstract】 Congenital adrenal hyperplasia (CAH) refers to a group of steroidogenic disorders in which an enzyme defect results in impaired synthesis of cortisol. The defects are transmitted as autosomal recessive traits. 21-Hydroxylase deficiency (21-OHD) is the most frequent type of CAH, which accounts for over 90% of patients with CAH. 21-OHD is generally categorized into three forms, i.e. salt wasting (SW), simple virilizing (SV) and nonclassic (NC). Salt wasting and simple virilizing forms are also called classic 21-OHD. The worldwide incidence of classic 21-OHD uncovered by the newborn screening programs was estimated to be 1 in 14,554 live birth for homozygotes, with the corresponding heterozygote (carrier) to be 1 in 61 persons and gene frequency to be 0.0082. The nonclassic 21-OHD is one of the most common autosomal recessive disorders, with the frequency ethnic-specific.By far in China, neither much research has been reported, nor much is known about the incidence, clinical or genetic features of 21-OHD. The objective of this study was to summarize the clinical features of 21-OHD cases managed in our hospital, investigate its genetic features, establish the clinically and prenatally practicable genetic diagnosis, explore the relationship between phenotype and genotype, and uncover if nonclassic 21-OHD patients were misdiagnosed as idiopathic hirsutism.Cases from October 1964 to September 1993 were retrospectively studied. Some of them and new cases were prospectively studied from September 1993 to November 1997. Data included patients’ sex,更多还原