摘要
目的对中国大陆地区婴儿期起病的早发型糖原贮积症Ⅱ型患者进行临床分析、基因突变分析及产前基因诊断。方法对2例婴儿期起病的糖原贮积症Ⅱ型患儿进行临床分析,并提取患儿及其父母的外周血DNA,应用聚合酶链反应(PCR)扩增α-1,4-葡萄糖苷酶基因(GAA)的19个外显子,直接测序,进行先证者及其父母的基因突变检测;在明确先证者基因突变后,对胎儿进行产前基因诊断。结果家系中2例患儿的发病时间均较早(第一胎男孩为1月+,第二胎女孩为2月),临床主要表现为心脏和骨骼肌受损的征象,以心肌和呼吸肌受累最为明显,患儿表现为明显的四肢肌张力低下,呼吸急促,口唇发绀,辅助检查提示患儿肌酸肌酶升高,胸部正位X片示心影增大,以心室为主,心脏超声示心脏明显增大,心肌肥厚。突变检测:GAA基因测序发现该家系先证者存在2个突变,分别为错义突变c.1935C>A(D645E)和无义突变c.1822C>T(R608*),其中后者为新突变,50例健康人对照100个等位基因测序未发现该位点的突变;羊水细胞GAA基因检测未发现该家系上述2个位点突变。结论婴儿期起病的糖原贮积症Ⅱ型患儿临床表现均较为严重,死亡率高,主要死亡原因为呼吸肌和心肌受累所导致的呼吸、心脏功能衰竭。本研究对一个糖原贮积症Ⅱ型家系进行了临床分析和基因诊断,明确了先证者发病的遗传学病因,并发现了一个新突变,为这个家庭的产前诊断和最终健康孩子的出生,打下了坚实的基础。
Objective：To carry out clinical,genetic and prenatal diagnosis for a family of the infantile-onset glycogen storage disease type II（GSD II,Pompe disease）.Methods：Two cases of infantile-onset glycogen storage disease type Ⅱ（GSDⅡ）children with clinical analysis,extraction of peripheral blood of children and their parents DNA,polymerase chain reaction（PCR）amplification of α-1,4- glucosidase gene（GAA）of 19 exons,direct sequencing,were the parents of the proband and gene mutation;in clear proband mutation after prenatal diagnosis of the fetus. Results：Two children in the family showed early onset of the clinical manifestations（the first was a boy in the first month,the second was a girl in the second month）,the main clinical manifestations of heart and skeletal muscle damage signs to cardiac and respiratory muscles the most obvious involvement,patients showed significant limb hypotonia,shortness of breath,cyanosis of lips,auxiliary examinations showed elevated creatine kinase,chest X ray and echocardiography shows significantly heart enlargement and cardiac hypertrophy. Mutation study revealed two mutations in this family,which were missense mutation c.1935C〉 A（D645E）and nonsense mutation c.1822C〉 T（R608 ＊）,and the latter was a new mutation,which was not found in 50 cases of healthy controls. The two mutations were not found in the amniotic fluid cells. Conclusion：The clinical manifestations of infantile-onset GSDⅡ were severe in children with high mortality,the major cause of death were respiratory and cardiac failure. In this study,we carried out clinical and genetic diagnosis in a glycogen storage disease type Ⅱ pedigree,and found a new mutation,which lay a solid foundation for prenatal diagnosis of this family.
出处
《中国优生与遗传杂志》
2015年第10期27-29,103,共4页
Chinese Journal of Birth Health & Heredity
