1例Angelman综合征合并眼皮肤白化病2型患者的临床和遗传学分析及文献回顾  

Clinical and molecular genetic analysis of Angelman syndrome with oculocutaneous albinism type 2:A case report and literature review

作　　者：周秋君 龚潘 焦莶如 杨志仙[1] ZHOU Qiu-jun;GONG Pan;JIAO Xian-ru;YANG Zhi-xian(Department of Pediatrics,Peking University First Hospital,Beijing 100034,China)

机构地区：[1]北京大学第一医院儿科,北京100034

出　　处：《北京大学学报（医学版）》2023年第1期181-185,共5页Journal of Peking University:Health Sciences

基　　金：国家自然科学基金(82171436);北京市自然科学基金(7202210);首都卫生发展科研专项(2020-2-4007)。

摘　　要：总结1例Angelman综合征(Angelman syndrome,AS)合并眼皮肤白化病2型(oculocutaneous albinism type 2,OCA2)患儿的临床诊疗过程及遗传学检测结果和特点,并以“Angelman综合征”“眼皮肤白化病2型”“Angelman syndrome”“Pgene”“Oculocutaneous albinism type 2”为关键词分别在CNKI、万方数据库及PubMed数据库(自建库至2019年12月)中检索,对国内外报道的AS合并OCA2病例进行汇总分析。本例患儿女,1岁,出生后即发现全身白,毛发色黄,眼球震颤,2个月会竖头,7个月会翻身,测头围42 cm,不能独坐,不会说话。家系全外显子组基因测序显示,患儿携带P基因c.168del(p.Gln58ArgfsTer44)纯合突变,经验证其父亲为杂合型,母亲为野生型。拷贝数变异检测提示,患儿母源染色体15q11.2-13.1区域缺失(P基因位于此区域内)。截至2019年12月,3个数据库中共检索到4篇相关文献,共报道了4例AS合并OCA2患儿,与本例一起进行汇总分析。AS合并OCA2患儿出生后均表现出皮肤白、毛发金黄、虹膜颜色浅,出生后6月龄左右发现全面发育迟缓,有2例随访至儿童期,语言始终无发育。4例患儿病程中出现癫痫发作,2例有共济失调,5例均有获得性小头畸形,2例白化病家族史阳性,3例完成脑电图监测结果均异常。遗传学检测结果显示,5例患儿均为母源性染色体15q11-13区域缺失,4例有父源15号染色体P基因突变,1例未进行P基因检测而根据临床诊断OCA2。AS合并OCA2病例相对少见,根据出生后明显的临床表现较容易获得OCA2临床诊断,当合并神经发育迟缓等临床表现时,提示早期临床难以诊断的AS可能,遗传学检测两者的交叉遗传现象可最终确诊此种复合病。To summarize the clinical diagnosis and treatment process and genetic test results and characteristics of one child with Angelman syndrome(AS)complicated with oculocutaneous albinism type 2(OCA2),and to review the literature.“Angelman syndrome”“P gene”and“Oculocutaneous albinism type 2”were used as keywords to search at CNKI,Wanfang,and PubMed databases(from creation to December 2019).Then all the patients were analyzed.The patient in this study was a girl aged 1 year.After birth,she was found to present as white body,yellow hair,and nystagmus.She could raise her head at the age of 2 months and turn over at the age of 7 months.The head circumference was 42 cm and she could not sit alone or speak at present.Trio-based exome sequencing revealed that the patient carried a homozygous mutation of c.168del(p.Gln58ArgfsTer44)in the P gene,and her father was heterozygous and her mother was wild-type.The detection of copy number variation showed deletion on the maternal chromosome at 15q11.2-13.1 region(P gene located in this region)in the patient.Until December 2019,a total of 4 cases in the 4 literature had been reported.Adding our case here,the 5 cases were summarized and found that all the cases showed white skin,golden hair,and shallow iris after birth.Comprehensive developmental delay was found around 6 months of age after birth,and the language remained undeveloped in 2 cases till follow-up into childhood.Seizures occurred in 4 patients.Two cases had ataxia.All the 5 cases had acquired microcephaly.Two cases had a family history of albinism.Electroencephalogram monitoring was completed in 3 cases and the results were abnormal.Genetic tests showed that all the 5 cases had deletion on maternal chromosome at 15q11-13 region.Four cases carried mutation of P gene on paternal chromosome.And 1 case was clinically diagnosed as OCA2 without P gene test.AS combined with OCA2 is relatively rare.OCA2 is easily diagnosed based on the obvious clinical manifestations after birth.When combined with clinical manifestati

关 键 词：ANGELMAN综合征 眼皮肤白化病 P基因 突变 

分 类 号：R596[医药卫生—内科学]