甲基化方法诊断3例Prader-Willi综合征

Diagnosis of Prader-Willi syndrome with methylation test

目的为临床怀疑Prader-Willi综合征(PWS)的患者建立快速准确的分子诊断方法,有利于早期治疗。方法对门诊以肥胖和智力落后就诊的6例患者,根据2001年Meral等提出的临床诊断PWS标准,将3例完全符合临床诊断标准归为高度怀疑组,另3例不完全符合临床诊断标准归为低度怀疑组。用甲基化特异性酶消化患者DNA后,同时扩增15 q 11.2-13位置SNRPN基因的1号外显子和内参照基因H19。结果3例高度怀疑者均确诊为PWS,均有典型PWS表现,如新生儿期严重肌张力低下,喂养困难,1岁后肌张力好转,食欲增大,肥胖,轻中度智力落后及特殊面容。另3例低度怀疑的患者有智力落后和肥胖,但无新生儿期严重肌张力低下和喂养困难者,排除了PWS诊断。结论甲基化方法结果与临床诊断吻合度高。在临床高度怀疑PWS时,建议用甲基化方法快速确诊,以使患儿能得到及时治疗。[临床儿科杂志,2007,25(12):996-998]

Objectives To set up a fast and easy genetic test for patients with clinically suspected of PraderWilli syndrome and facilitate early diagnosis and early intervention for these patients. Methods Six patients with obesity and mental retardation were classified into two groups ,group with high index of suspicion and group of low index of suspicion according to the criteria proposed by Meral et al in 2001. Patients＇DNA was processed with methylation-dependent digestion with Hpa Ⅱ and McrBC. Exon 1 of the SNRPN gene was amplified together with a control sequence of H19 for each DNA sample. Results After digestion by McrBC,only the control sequence of H19 could be amplified. Exon 1 of the SNRPN gene could not be amplified after McrBC digestion in PWS patients. Three patients from the high risk group were confirmed as PWS while the low risk group patients were ruled out of PWS with this method. Hypotonia during neonatal time,feeding difficulties were the typical manifestation of highly suspected patients. The muscle tone and appetite had improved,and they became obesity,mild to medium mental retarded and showed peculiar face after 1 year old. Other 3 patients had mental retardation and obesity,but without hypotonia and feeding fifficuhies. Conclusions Methylation test has been proven as useful test for the diagnosis of PWS,suggesting that it can be used to diagnose the patients with suspected of Praeer-Willi syndrome and assure them get intervintion timely.