CAJ | 학술논문

目的对临床诊断的Angelman综合征(AS)患儿进行遗传学诊断和临床特点分析.方法利用MS-PCR、STR家系连锁分析和染色体核型分析,对17例临床诊断AS的患儿(其中男7例,女10例,年龄8个月～5岁)进行遗传学诊断.依据国际诊断标准,分析15q11-13缺失型AS患儿的相关表型特点.结果 (1)17例确诊为15q11-13缺失型AS.(2)患儿出生情况无明显异常.所有的患儿均有不同程度的运动和语言发育迟缓,以语言发育落后更为显著,并伴有特征性的快乐行为.(3)AS的经常性表现:癫癎(15例),异常脑电图(14例),发生率约80%～90%,只有35%的患儿(6例)存在小头畸形.(4)与AS较为关联的表现:平枕/枕骨凹陷(12例),下颌突出(10例),宽嘴和齿缝稀疏(13例),频繁流口水(8例),过多的嘴部动作(9例),肤色及发色浅淡(13例),运动时屈曲手臂(9例),睡眠障碍(9例)等,发生率47%～77%.＞2岁年龄组患儿的AS相关性表现的发生率均高于≤2岁年龄组患儿.结论联合应用MS-PCR、STR连锁分析和染色体核型分析,确诊17例患儿为15q11-13缺失型AS.我国15q11-13缺失型AS患儿的临床表现与国际诊断标准基本一致,惟小头畸形比率低于白种人,可能存在人种表型差异.随着年龄的增长AS相关性表现更为明显.
목적 대림상진단적Angelman종합정(AS)환인진행유전학진단화림상특점분석.방법 이용MS-PCR、STR가계련쇄분석화염색체핵형분석,대17례림상진단AS적환인(기중남7례,녀10례,년령8개월～5세)진행유전학진단.의거국제진단표준,분석15q11-13결실형AS환인적상관표형특점.결과 (1)17례학진위15q11-13결실형AS.(2)환인출생정황무명현이상.소유적환인균유불동정도적운동화어언발육지완,이어언발육락후경위현저,병반유특정성적쾌악행위.(3)AS적경상성표현:전간(15례),이상뇌전도(14례),발생솔약80%～90%,지유35%적환인(6례)존재소두기형.(4)여AS교위관련적표현:평침/침골요함(12례),하합돌출(10례),관취화치봉희소(13례),빈번류구수(8례),과다적취부동작(9례),부색급발색천담(13례),운동시굴곡수비(9례),수면장애(9례)등,발생솔47%～77%.＞2세년령조환인적AS상관성표현적발생솔균고우≤2세년령조환인.결론 연합응용MS-PCR、STR련쇄분석화염색체핵형분석,학진17례환인위15q11-13결실형AS.아국15q11-13결실형AS환인적림상표현여국제진단표준기본일치,유소두기형비솔저우백충인,가능존재인충표형차이.수착년령적증장AS상관성표현경위명현.
Objective Angelman syndrome (AS) is a neurodevelopmental genetic disorder that maps to 15q11-13. The primary phenotypes are attributable to loss of expression of imprinted UBE3A gene within this region which can arise by means of a number of mechanisms. The purpose of this study was to make a genetic diagnosis and to analyze the clinical features in suspected patients with AS. Method A total of 17 cases were diagnosed clinically as AS including 7 males and 10 females. The age at the time of diagnosis ranged from 8 months to 5 years. Genetic diagnosis was made by methylation-specific PCR ( MS-PCR), linkage analysis by short tandem repeat (STR) and chromosome karyotype analysis. According to the international diagnostic criteria of AS, the related characteristic clinical features of the AS patients with deletion of 15q11-13 were analyzed and summarized. Result Deletion of 15q11-13 was confirmed by genetic diagnosis in 17 AS patients. No abnormal findings were observed when they were born.Developmental delay in movement, speech impairments and happy disposition were observed in 100% ( 17/17 )AS patients. And the severe speech deficit was much easier and more obvious to observe than movement.About 80% (14/17) -90% (15/17) AS patients presented frequent clinical characteristics, such as seizures and abnormal EEG. However, microcephaly could only be observed in 35% ( 6/17 ) AS patients.Regarding the associated findings of AS, 41% (7/17) -77% (13/17) AS patients could be observed with flat occiput/occipital groove, prognathia, wide mouth, wide-spaced teeth, frequent drooling, excessive mouth behaviors, hypopigmented skin, light hair compared to parents, flexed arm position during ambulation and sleep disorder etc. These features occurred at a higher frequency in those patients of ＞ 2 years old group than that of ＜ 2 years old group. Conclusion The testing strategies of MS-PCR and STR linkage analysis combined with chromosome karyotype analysis were appropriate to the molecular genetic diagnosis of AS. In our analysis of clinical features, there was a lower rate of small head circumference (HC) in 35% patients compared with 80% patients in Caucasian with microcephaly, which might be attributable to the phenotypic heterogeneity in different races. And the birth history, movement and speech development and main clinical features of the Chinese AS patients were consistent with those of other studies. Clinical analysis in patients of different age groups showed that findings associated with AS would be more easily observed with the age increasing. Genetic diagnosis should be performed in clinically suspected AS patients.