三个Xp21临近基因缺失综合征家系的临床特征和遗传学分析  

Clinical characteristics and genetic analysis of three pedigrees with Xp21 adjacent gene deletion syndrome

作　　者：车凤玉 王丽芳[2] 铁晓玲 朱巧棉 张李钰 杨颖[1] CHE Fengyu;WANG Lifang;TIE Xiaoling;ZHU Qiaomian;ZHANG Liyu;YANG Ying(Shaanxi Institute for Pediatric Diseases,Xi’an Children’s Hospital,Xi’an,Shaanxi 710002,China;Department of Child Health Care,Xi’an Children’s Hospital,Xi’an,Shaanxi 710002,China;Department of Rehabilitation,Xi’an Children’s Hospital,Xi’an,Shaanxi 710002,China;Neonatal Intensive Care Unit,Xi’an Children’s Hospital,Xi’an,Shaanxi 710002,China)

机构地区：[1]西安市儿童医院/陕西省儿科疾病研究所,陕西西安710002 [2]西安市儿童医院儿童保健科,陕西西安710002 [3]西安市儿童医院康复科,陕西西安710002 [4]西安市儿童医院新生儿重症医学科,陕西西安710002

出　　处：《中国优生与遗传杂志》2022年第10期1828-1832,共5页Chinese Journal of Birth Health & Heredity

基　　金：陕西省创新能力支撑计划(2019KJXX-055);西安市儿童医院院级课题(2020A07)。

摘　　要：目的 探讨分析三个不相关的Xp21临近基因缺失综合征家系患儿的遗传学特点,辅助疾病早期诊断。方法 收集3个无血缘关系的Xp21临近基因缺失综合征患儿的临床表型、家族史和相关生化检查结果,采用全外显子组测序、基因芯片和多重连接探针扩增技术(MLPA)对来自3个家庭的4名患儿和1例流产组织进行遗传学分析。结果 本研究3个家系4名患儿均为新生儿期起病的男性患者,其临床特征因受累区域基因缺失大小范围和所包含基因的数量和功能的不同而有所差异,其中家系2的两个同胞兄弟均于新生儿期因肾上腺危像死亡;家系1和3的患儿均表现为不同程度的精神运动发育落后,且家系3患儿除典型的ACH-GK-DMD临床表型外还表现有面容异常和耳聋等症状;3个家系患儿及家系3的胎儿流产组织基因检测结果均提示为Xp21临近基因缺失综合征,家系3还同时合并22q11.21重复变异。结论 对于临床高度疑似Xp21临近基因缺失综合征的患儿,合适的遗传学检测方法可以为临床提供快捷的诊断思路。该疾病表型复杂多样,易被漏诊,需要结合生化检查及基因分析综合诊断。Objective To explore and analyze the genetic features of 3 unrelated pedigrees with Xp21 contiguous gene deletion syndrome, and to assist the early diagnosis of the disease. Methods Clinical characteristics, family history and biochemical indexes of 3 patients with Xp21 contiguous gene deletion syndrome were collected. Whole exome sequencing,chromosomal microarray and multiplex ligation-dependent probe amplification(MLPA) were carried out to analyze the genetic features of 4 patients from 3 pedigrees. Results All the 4 cases reported in this research were males, whose clinical symptoms were slightly different depending on the loci involved,but all of them were with a neonatal onset. The two siblings from family 2 died of adrenal crisis in the neonatal period. Patients from family 1 and 3 showed different degrees of psychomotor delay. Moreover, patients from family 3 also showed facial abnormalities and deafness in addition to the typical clinical phenotype of AHC-GKD-DMD. In addition to the Xp21 deletion, the proband of family 3 also carried a 22q11.2 microduplication, whereas the aborted fetus in family 3 was 45,X. Conclusion Appropriate genetic tests should be used to promptly diagnose individuals with Xp21 deletion. Due to the complex genotypes and diverse phenotypes of this syndrome, a combination of biochemical and molecular analyses is required.

关 键 词：Xp21临近基因缺失综合征 先天性肾上腺功能减退 DMD 甘油激酶缺乏症 遗传学检测 

分 类 号：R725.9[医药卫生—儿科]