Xp21邻近基因缺失综合征家系分析并文献复习  

Pedigree analysis of Xp21 contiguous gene deletion syndrome and literature review

作　　者：郑雅玲 陈云娥 林宝花 刘登礼[2] 陆妹 Zheng Yaling;Chen Yun′e;Lin Baohua;Liu Dengli;Lu Mei(Department of Pediatrics,Women and Children′s Hospital,School of Medicine,Xiamen University,Xiamen 361003,Fujian Province,China;Department of Pediatrics,the First Affiliated Hospital of Xiamen University,Xiamen 361003,Fujian Province,China)

机构地区：[1]厦门大学附属妇女儿童医院,厦门市妇幼保健院儿科,361003 [2]厦门大学附属第一医院儿科,361003

出　　处：《中华实用儿科临床杂志》2020年第9期695-699,共5页Chinese Journal of Applied Clinical Pediatrics

基　　金：国家重点研发计划(2017YFC1001700);厦门市科技计划指导性项目(3502Z20199078)。

摘　　要：目的:探讨Xp21邻近基因缺失综合征的临床特征和遗传学特点,提高临床医师对该病的认识。方法:对Xp21邻近基因缺失综合征一家三兄弟的临床表现、诊治过程、基因特点等进行分析。以"Xp21邻近/临近基因缺失综合征"、"复合型甘油激酶缺乏症"和"Xp21 contiguous gene deletion syndrome"、"complex glycerol kinase deficiency"为关键词,分别对中国知网、维普数据库、万方数据和生物医学文献数据库(PubMed)及Web of Science数据库自建库至2019年12月收录的文献进行检索,并复习相关资料。结果:先证者为男童,第4胎,第4产,在新生儿期因"皮肤色素沉着、促肾上腺皮质激素显著升高"诊断为"先天性肾上腺皮质增生症(失盐型)",患儿血清三酰甘油、肌酸激酶水平显著升高,尿甘油酸水平显著升高,17羟孕酮水平正常,经微阵列单核苷酸多态性分析技术分析发现患儿X染色体p21.3p21.1区域5.16 Mbp缺失,确诊Xp21邻近基因缺失综合征,予氟氢可的松、氢化可的松替代治疗,患儿皮肤颜色转为正常,血清促肾上腺皮质激素降至正常。现患儿3岁8个月,智力运动发育落后,腓肠肌假性肥大,无电解质紊乱。患儿父母健康,患儿姐姐18岁,健康;患儿长兄及次兄均在出生不久后皮肤颜色变黝黑、智力运动落后,外院诊断为"脑性瘫痪、肌肉萎缩",分别于1岁及1岁6个月死亡。患儿母亲及姐姐X染色p21.3p21.1区带杂合缺失。文献检索共收集到22例资料完整、基因诊断明确的国内外个案报道,其中13例于新生儿期起病,主要表现为肾上腺皮质功能不全、肌营养不良、高三酰甘油血症、发育迟缓等,少数有特殊面容;Xp21区域大片段缺失变异,主要缺失基因均包括NR0B1、GK和DMD。结论:Xp21邻近基因缺失综合征临床表型复杂,且易被误诊,在新生儿期即可发生肾上腺皮质功能不全,预后不良,需要通过血清生化及基因分析明确诊断。Objective To explore the clinical and genetic features of Xp21 contiguous gene deletion syndrome,in order to improve clinicians′understanding of the disease.Methods The clinical manifestations,diagnosis and treatment process as well as genetic characteristics of 3 brothers from 1 family with Xp21 contiguous gene deletion syndrome were studied.Literatures were retrieved with key words including"Xp21 contiguous gene deletion syndrome"and"complex glycerol kinase deficiency"in CNKI,VIP database,Wanfang database,Biomedicine Literature database(PubMed)and Web of Science from the database establishment to December 2019,and the relevant features were reviewed.Results The surviving proband was a boy,the fourth child and the fourth birth.He was suspected as congenital adrenal hyperplasia(salt-losing type)because of significant hyperpigmentation and obviously increased plasma adrenocorticotropic hormone(ACTH)in the neonatal period.Serum triglyceride and creatine phosphokinase were elevated,and urine analysis revealed massive glyceroluriam in this patient.But his serum 17-hydroxyprogesterone was normal.5.16 Mbp deletion in Xp21.3p21.1 was detected by single nucleotide polymorphisms,and the diagnosis of Xp21 contiguous gene deletion syndrome was confirmed.After the supplements of hydrocortisone and fludrocortisone,pigmentation was improved,and the serum ACTH became normal.Now,the patient was 3 years and 8 months old,having pseudomuscle hypertrophy,intellectual and language developmental delay,but no the electrolyte disorder.His parents and 18-years-old sister were healthy.While his two elder brothers who were suspected as cerebral palsy and muscular atrophy due to the symptoms of dark skin color and psychomotor development delay after birth died at the age of 1 year and 1.5 years,respectively.Deletions in Xp21.3p21.1 region were found in his mother and elder sister.A total of 22 cases with full and complete clinical data and definite genetic diagnosis were collected from domestic and foreign literature,and 13 cases of them

关 键 词：Xp21邻近基因缺失综合征 先天性肾上腺皮质功能不全 高甘油三酯血症 肌营养不良 

分 类 号：R725.9[医药卫生—儿科]