摘要
目的 探讨一个X连锁肾上腺发育不良家系的临床特点和分子发病机制.方法 收集就诊于广州军区广州总医院内分泌代谢科的一个X连锁先天性肾上腺发育不良家系的临床表现、治疗及随访结局等资料.用二代测序结合Sanger法验证对家系患者进行DAX1基因突变分析.结果 家系7例患者中3例均于1岁内发病、青春期前死亡.4例存活患者有典型肾上腺发育不良及低促性腺激素性性腺功能低下的临床和激素改变,均需超生理量氢化可的松替代;3例成人患者替代治疗后男性化,但精子生成不理想.4例存活患者均存在DAX1基因c.827A>C(p.Gln276Pro)变异,PolyPhen 2预测有害.结论 DAX1基因c.827A>C(p.Gln276Pro)变异可能是该家系先天性肾上腺发育不良和低促性腺激素性性腺功能低下的致病原因.
Objective To report on the clinical pictures of 7 patients from a pedigree affected with X-linked adrenal hypoplasia congenita(XL-AHC)and hypogonadotropic hypogonadism(HH)and the underlying mutations.Methods Seven patients were identified from a four-generation pedigree affected with XL-AHC and HH.Their clinical features,endocrinological changes,treatment and drug response were recorded.The patients were subjected to next-generation sequencing,and the result was verified by Sanger sequencing.PolyPhen-2 was used for predicting the influence of the mutation on protein production.Results Three deceased patients had manifested adrenal insufficiency(AI)within one year after birth.Two died at 6 and one died at 12.The four survivors presented with salient clinical and endocrinological features of AHC and HH,adrenal and testicular atrophy,and renin-angiotensin compensation.Two adult patients had testicular micro-stone detected by ultrasound.One of them also had remarkable seminiferous tubule degeneration by biopsy.The patients were followed up for 0.5 to 10 years.All required hyper-physiological dose of hydrocortisone to stabilize their clinical condition.In three patients,gonadotropic or androgen replacement induced cardinal masculine development but with unsatisfactory testis growth and sperm production.Genetic analysis revealed a novel missense c.827A>C(p.Q276P)mutation in a hotspot region within a highly conserved domain.PolyPhen-2 predicted the mutation to be highly hazardous.Conclusion The novel p.Q276P mutation of the DAX1 gene probably underlies the XL-AHC and HH in this pedigree with variable clinical presentations in the patients.
作者
尹卓娜
金文胜
许卫国
李红梅
张松
彭玲玲
陈晓东
彭光明
韩立新
Yin Zhuonal,;Jin Wensheng;Xu Weiguo;Li Hongmei;Zhang Song;Peng Lingling;Chen Xiaodong;Peng Guangming;Han Lixin(Department of Endocrinology,Guangzhou General Hospital of PLA,Guangzhou,Guangdong510010,China;Department of Endm rinology,the Second People’s Hospital of Guangdong Province,Guangzhou,Guangdong,510317,China;Department of Elderly Endorinology,Guangzhou Generral Hospital of PLA,Guangzhou,Guangdong510010,China;Department of Pharmacy,GuangzhouGeneral Hospital of PLA,Guangzhou,Guangdong510010,China;Department of Pathology,Guangzhou General Hospital of PLA,Guangzhou,Guangdong510010,China;Department ofComputer Tomography,GuangzhouGeneral Hospital of PLA,Guangzhou,Guangdong510010,China;Department of MRJ,Guangzhou General Hospital of PLA,Guangzhou,Guangdong510010,China)
出处
《中华医学遗传学杂志》
CAS
CSCD
2019年第5期456-461,共6页
Chinese Journal of Medical Genetics
