一个肌-眼-脑病家系的临床表型和POMGNT1基因突变分析

Clinical and mutation analysis of a Chinese family with muscle-eye-brain disease

目的分析并确立1个肌-眼-脑病（muscle—eye—brain disease，MEB）家系的临床表型及POMGNT1基因突变的类型。方法收集肌-眼-脑病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，用聚合酶链反应（polymerase chain reaction，PCR）扩增POMGNT1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。结果该患儿诊断为松软儿，生后起病，智力运动发育落后，肌病面容，肌酶中度升高，头颅MRI提示前头部多小脑回，后头部无脑回畸形，脑白质异常信号，脑于、小脑发育不良及小脑囊肿，临床诊断为先天性肌营养不良伴眼脑病变。基因检测显示患儿POMGNT1基因第22外显子5’端前第1个碱基发生了改变（C．1896-1 G〉C），推测该突变可能导致剪切错误；而在第16外显子也发生了c．1319T〉G，P．L440R错义突变。其父母分别为此位点杂合突变。结论通过分子遗传学分析发现该患儿为POMGNT1基因的复合杂合突变，其突变基因分别来自父母，符合肌-眼-脑病常染色体隐性遗传的规律，可确诊为肌-眼-脑病。

Objective To study the clinical feature of a Chinese family with muscle-eye-brain disease （MEB） and the mutation of protein O-linked-mannose beta-1, 2-N-acetylglucosaminyltransferase I gene （POMGNT1）. Methods Clinical data of the proband and his family members were collected. Genomic DNA from the patient and his parents was extracted using standard procedures from the peripheral blood leukocytes. Polymerase chain reaction and DNA direct sequencing were employed to analyze all of the exons to determine the mutation, and the relationship between genotype and phenotype was analyzed. Results The proband was diagnosed as floppy baby, presented with delayed psychomotor development and myopathic face. His serum creatine kinase （CK） level elevated moderately and brain MRI showed cerebral and cerebellar gyrus abnormalities with white matter signal intensity changes, cerebellar cysts and cerebellar and brain stem hypoplasia, consistent with congenital muscular dystrophy with eye-brain disorder. Further test with DNA detected a compound heterozygous mutation of c. 1896-1 G〉C before exon 22 which may induce splicing error, and missense mutation c. 1319T〉G, p. L440R in exon 16. Both parents had a heterozygous mutation at the mutation sites. Conclusion According to our study, the family is diagnosed as MEB. The proband carried compound heterozygous mutations in the POMGNT1 gene, and his parents are heterozygous carriers, which is consistent with autosomal recessiv inheritance. The child is definitely diagnosed as having muscle-eye-brain disease.