摘要
目的 明确 3例Wiskott Aldrich综合征 (WAS)患儿WAS蛋白 (WASP)基因突变的类型。方法 根据典型临床表现 (血小板减少、湿疹、反复感染 ) ,及淋巴细胞和血小板扫描电镜改变 ,采用PCR直接测序法 ,对 3例疑为WAS的患儿及其母亲的WASP基因进行序列分析。结果 以正义、反义引物扩增的PCR产物分别测序 ,发现两种新型WASP基因突变 :2例WAS孪生兄弟WASP基因第 10外显子 ,第 984位核苷酸C缺失突变 (984delC) ,导致 317位密码子后移码突变 ,于 4 4 4位密码子提前出现终止密码 (H317fsX4 4 4 ) ;其母亲为此突变WASP基因携带者。另 1例WAS患儿WASP基因第 11外显子 ,第 1388位核苷酸由G替换为T(1388G→T) ,为无义突变 ,使第 4 5 2位密码子提前变为终止密码(E4 5 2X)。其母亲无此突变WASP基因。结论 鉴定出两种新型WASP基因突变 ,WASP基因序列分析对于不典型和散发WAS的诊断及WASP突变基因携带者的检出有重要作用。
Objective The Wiskott-Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency caused by mutations in the WAS protein (WASP) gene. The disease is characterized by recurrent infections, eczema, and thrombocytopenia with small platelets, and it is known to be associated with extensive clinical variability, and mutation studies indicated that genotypes are also highly variant among WAS patients. The present study was conducted to identify the mutation types of Wiskott-Aldrich syndrome protein (WASP) gene in 3 boys suffering from Wiskott-Aldrich syndrome. Methods Based on the typical clinical manifestations of Wiskott-Aldrich syndrome including thrombocytopenia, eczema, and recurrent infections and scanning electron micrographs, 3 patients were suspected of having WAS. The WASP gene of the 3 patients and their mothers were detected by PCR-direct sequencing analysis. Results By sequence analysis using sense and antisense primer separately, the authors found two novel WASP gene mutations. For the twin brothers, a C deletion at nucleotide 984 was detected in exon 10 of WASP gene (984delC). The consequence of the C deletion involved frameshift mutation after H317 and premature stop at 444 (H317fsX444). Their mother was a carrier of the mutated WASP gene. For another WAS patient, a nonsense mutation with nucleotide substitution of G to T at position 1388 (1388G→T) in exon 11 of WASP gene, led to premature translational termination at amino acid position 452 (E452X). His mother had not been found to have WASP gene mutation. Conclusion Genetic analysis is useful in definite diagnosis of Wiskott-Aldrich syndrome patients and in carrier detection and prenatal diagnosis, especially of atypical or sporadic WAS patients.
出处
《中华儿科杂志》
CAS
CSCD
北大核心
2003年第8期590-593,T002,共5页
Chinese Journal of Pediatrics
