Walker—Warburg综合征的临床表型与POMT1基因突变分析

Clinical and genetic analysis of a Chinese family with Walker-Warburg syndrome

目的分析1例临床诊断为Walker—Warburg综合征（WWS）患儿的临床及遗传学特征。方法收集该例患儿及父母的临床资料，提取患儿及其父母外周血基因组DNA，聚合酶链反应（PCR）扩增与此类疾病相关的5个候选基因包括POM1、POMT2、POMGnT1、胀州、州矾P基因的外显子，以琼脂糖凝胶电泳鉴定PCR产物，PCR产物纯化后DNA直接测序，确定基因突变的类型，分析基因型和表型的关系。结果该患儿自幼智力运动发育落后，肌力、肌张力低下，早期出现关节挛缩，肌酸激酶中度升高，眼科检查疑诊青光眼，头颅核磁共振示侧脑室扩大，小脑、脑干发育不良，胼胝体发育不良，小脑囊肿，临床诊断为先天性肌营养不良伴眼脑畸形。进一步基因检测示患儿POMT1基因第5外显子发生了C．313C〉T，P．Arg105Cys的错义突变，来自其父亲，第20外显子发生了e．2208delG，P．Trp736X的移码突变，来自其母亲。该患儿的2个突变均为已报道致病突变。结论通过分子遗传学分析发现该患儿为POMT1基因的复合杂合突变，其突变基因分别来自其父母，符合WWS常染色体隐性遗传的特点，从基因水平可诊断为WWS，可为家庭提供遗传咨询和产前诊断。

Objective To analyze the clinical, molecular and genetic features of a Chinese family with Walker- Warburg syndrome（WWS）. Methods The clinical data of the proband and his family members were collected. Ge- nomic DNAs from the patient and his parents were extracted with standard procedures from the peripheral blood leuko- cytes. Polymerase chain reaction and DNA direct sequencing were employed to analyze all of the 20 exons of the POMT1 gene to determine the mutation, and the relationship between genotype and phenotype was analyzed. Results The proband presented with delayed psychomotor development, muscle hypotonia and early joint contractures, his serum creatine kinase was elevated moderately and the brain magnetic resonance imaging （MRI） displayed brain structural malformations,cerebellar cyst, bilateral dilatation of the lateral ventricle, cerebellum and brainstem dysplasia. Further genetic testing detected a compound heterozygous mutation of c. 313C 〉 T, p. Arg105Cys inherited from his father, a frameshift mutation c. 2208delG, p. Trp736X inherited from his mother, both of which were known as pathogenic mutations. Conclusions According to the study, the proband carried compound heterozygous mutation of POMTI gene, and his parents were heterozygous carriers,which is consistent with autosomal recessive inheritance. The child is defi- nitely diagnosed as WWS. Genetic counseling and prenatal diagnosis are available for this family.