CAJ | 학술논문

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,脑干、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.
목적 분석병학립1개기-안-뇌병( muscle-eye-brain disease,MEB)가계적림상표형급POMGNT1기인돌변적류형.방법 수집기-안-뇌병환인급부모적림상자료,제취환인급기부모외주혈기인조DNA,용취합매련반응(polymerase chain reaction,PCR)확증POMGNT1기인적외현자,이경지당응효전영감정PCR산물,PCR산물순화후DNA직접측서,학정기인돌변적류형,분석기인형화표형적관계.결과 해환인진단위송연인,생후기병,지력운동발육락후,기병면용,기매중도승고,두로MRI제시전두부다소뇌회,후두부무뇌회기형,뇌백질이상신호,뇌간、소뇌발육불량급소뇌낭종,림상진단위선천성기영양불량반안뇌병변.기인검측현시환인POMGNT1기인제22외현자5′단전제1개감기발생료개변(c.1896-1 G＞C),추측해돌변가능도치전절착오；이재제16외현자야발생료c.1319T＞G,p.L440R착의돌변.기부모분별위차위점잡합돌변.결론 통과분자유전학분석발현해환인위POMGNT1기인적복합잡합돌변,기돌변기인분별래자부모,부합기-안-뇌병상염색체은성유전적규률,가학진위기-안-뇌병.
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 1 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.