[1]牛国辉,张晓莉,李林琛,等.佩利措伊斯-梅茨巴赫病临床及遗传学特征分析[J].新乡医学院学报,2022,39(2):122-126.[doi:10.7683/xxyxyxb.2022.02.004]
　NIU Guohui,ZHANG Xiaoli,LI Linchen,et al.Clinical and genetic characteristics of Pelizaeus-Merzbache disease[J].Journal of Xinxiang Medical University,2022,39(2):122-126.[doi:10.7683/xxyxyxb.2022.02.004]
点击复制

佩利措伊斯-梅茨巴赫病临床及遗传学特征分析
分享到：

《新乡医学院学报》[ISSN:1004-7239/CN:41-1186/R]

卷:
39
期数:
2022年2
页码:
122-126
栏目:
临床研究
出版日期:
2022-02-05

文章信息/Info

Title:
Clinical and genetic characteristics of Pelizaeus-Merzbache disease
作者:
牛国辉1; 张晓莉2; 李林琛1; 刘红星1; 崔　博1; 王　鑫1; 谢加阳1; 贾天明2
（1.郑州大学第三附属医院儿童康复科，河南　郑州　450052；2.郑州大学第三附属医院小儿神经内科，河南　郑州　450052）
Author(s):
NIU Guohui1; ZHANG Xiaoli2; LI Linchen1; LIU Hongxing1; CUI Bo1; WANG Xin1; XIE Jiayang1; JIA Tianming2
(1.Department of Children Rehabilitation,the Third Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,Henan Province,China;2.Department of Pediatric Neurology,the Third Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,Henan Province,China)
关键词:
佩利措伊斯-梅茨巴赫病; 临床特征; 蛋白脂蛋白1基因; 基因突变
Keywords:
Pelizaeus-Merzbache disease; gene detection; proteolipid protein 1 gene; gene mutation
分类号:
R742
DOI:
10.7683/xxyxyxb.2022.02.004
文献标志码:
A
摘要:
目的　探讨佩利措伊斯-梅茨巴赫病（PMD）的临床及分子遗传学特征。方法　回归性分析2015年6月至2020年10月郑州大学第三附属医院确诊的12个家系共14例PMD患儿的临床表现和基因突变特点。结果　14例均为男性，就诊年龄5 d至10岁，起病年龄1 d至7个月。首发症状表现为眼球震颤9例，大运动发育迟缓3例，呻吟样呼吸、哭声弱1例，异常姿势2例。临床表现：14例均存在发育迟缓，其中10例以运动发育迟缓更为明显；肌张力低下10例，肌张力增高3例；12例存在眼球震颤。临床分型经典型8例，先天型2例，中间型4例。14例患儿头颅磁共振成像（MRI）均表现为脑白质髓鞘化障碍，脑干听觉诱发电位检测异常7例。14例先证者中，7例蛋白脂蛋白1（PLP1）基因为2~8 号外显子重复变异；1例为X染色体Xq22.2处重复0.33Mb区域，覆盖了PLP1基因100%的区域；1例c.83G>A变异，1例c.226G>C变异，2例c.259delC变异，2例c.157dupA变异。12例先证者为遗传性突变，均为母源遗传，母亲为无临床症状的携带者。c.83G>A、c.226G>C、c.259delC、c.157dupA均为国际上未报道的新突变。结论　PMD的首发症状以眼球震颤最为常见；发育迟缓、肌张力异常、眼球震颤为其最常见的临床症状；头颅MRI提示脑白质髓鞘化障碍。PLP1基因突变中重复变异最多，其次为点突变，c.83G>A、c.226G>C、c.259delC、c.157dupA变异为尚未报道的新突变。
Abstract:
Objective　To investigate the clinical and genetic features of Pelizaeus-Merzbache disease(PMD).Methods　The clinical manifestations and genetic mutation characteristics of 14 children with PMD from 12 families admitted to the Third Affiliated Hospital of Zhengzhou University from June 2015 to October 2020 were respectively analyzed.Results　All of the 14 children were male,the age ranged from 5 days to 10 years.The onset age was from 1 day to 7 months.The first symptoms were nystagmus in 9 children,gross motor development delay in 3 children,moaning breathing and weak crying in 1 child,and abnormal postures in 2 children.Clinical manifestations:14 patients had developmental delay,10 children had more obvious motor developmental delay.There were 10 children of hypotonia,3 children of hypertonia.Nystagmus was present in 12 children.The clinical classification included 8 cases of classic forms,2 cases of connatal forms,and 4 cases of transition forms.The brain magnetic resonance imaging(MRI) showed white matter myelination disorder in all of the 14 children.There were abnormalities in brainstem auditory evoked potentials in 7 children.Among the 14 children,7 children had duplication mutations in exon 2-8 of protein lipoprotein 1(PLP1) gene,1 child had a 0.33 Mb repeat region on Xq22.2 of the X chromosome(covering 100% of the PLP1 gene),1 child had c.83G>A variant,1 child had c.226G>C variant,2 children had c.259Del C variant,and the other 2 children had c.157Dup A variant.All of the 12 probands had genetic mutation,which were inherited from their mothers,and their mothers were asymptomatic carriers.c.83G>A,c.226G>C,c.259Del C and c.157Dup A were new mutations that had not been reported internationally.Conclusion　Nystagmus was the most common first symptom of PMD.Developmental delay,dystonia and nystagmus were the most common clinical symptoms.Brain MRI showed white matter myelination disorder.Duplication mutations was the most common in PLP1 gene,followed by point mutations.c.83G>A,c.226G>C,c.259delC and c.157dupA were new mutations that had not been reported.

参考文献/References:

［1］　INOUE K.Pelizaeus-merzbacher disease:molecular and cellular pathologies and associated phenotypes［J］.Adv Exp Med Biol,2019,1190:201-216.
［2］　OSRIO M J,GOLDMAN S A.Neurogenetics of pelizaeus-merzbacher disease［J］.Handb Clin Neurol,2018,148:701-722.
［3］　BAHRAMBEIGI V,SONG X,SPERLE K,et al.Distinct patterns of complex rearrangements and a mutational signature of microhomeology are frequently observed in PLP1 copy number gain structural variants［J］.Genom Med,2019,11(1):80.
［4］　BALL R S.The gesell developmental schedules:arnold gesell (1880-1961)［J］.J Abnorm Child Psychol,1977,5(3):233-239.
［5］　RYAN J J,UMFLEET L G,KANE A.Stability of WISC-IV process scores［J］.Appl Neuropsychol Child,2013,2(1):43-46.
［6］　SCALA M,TRAVERSO M,CAPRA V,et al.Pelizaeus-merzbacher disease due to PLP1 frameshift mutation in a female with nonrandom skewed X-chromosome inactivation［J］.Neuropediatrics,2019,50(4):268-270.
［7］　MIYAMOTO Y,TANAKA M,ITO H,et al.Expression of kinase-deficient MEK2 ameliorates Pelizaeus-Merzbacher disease phenotypes in mice［J］.Biochem Biophys Res Commun,2020,531(4):445-451.
［8］　KIM D,AN H,FAN C,et al.Identifying oligodendrocyte enhancers governing Plp1 expression［J］.Hum Mol Genet,2021,30(23):2225-2239.
［9］　OSORIO M J,ROWITCH D H,TESAR P,et al.Concise review:stem cell-based treatment of Pelizaeus-Merzbacher disease［J］.Stem Cells,2017,35(2):311-315.
［10］　GRUENENFELDER F I,MCLAUGHLIN M,GRIFFITHS I R,et al.Neural stem cells restore myelin in a demyelinating model of Pelizaeus-Merzbacher disease［J］.Brain,2020,143(5):1383-1399.
［11］　NOBUTA H,YANG N,NG Y H,et al.Oligodendrocyte death in Pelizaeus-Merzbacher disease is rescued by iron chelation［J］.Cell Stem Cell,2019,25(4):531-541.
［12］　STUMPF S K,BERGHOFF S A,TREVISIOL A,et al.Ketogenic diet ameliorates axonal defects and promotes myelination in Pelizaeus-Merzbacher disease［J］.Acta Neuropathol,2019,138(1):147-161.
［13］　KAPOOR D,GARG D,SHARMA S.Emerging role of the ketogenic dietary therapies beyond epilepsy in child neurology［J］.Ann Indian Acad Neurol,2021,24(4):470-480.
［14］　ELITT M S,BARBAR L,SHICK H E,et al.Suppression of proteolipid protein rescues Pelizaeus- Merzbacher disease［J］.Nature,2020,585(7825):397-403.
［15］　LI H,OKADA H,SUZUKI S,et al.Gene suppressing therapy for Pelizaeus-Merzbacher disease using artificial microRNA［J］.JCI Insight,2019,4(10):e125052.
［16］　KOUGA T,KOIZUME S,AOKI S,et al.Drug screening for Pelizaeus-Merzbacher disease by quantifying the total levels and membrane localization of PLP1［J］.Mol Genet Metab Rep,2019,20:100474.
［17］　MARTEYN A,BARON-VAN E A.Is involvement of inflammation underestimated in Pelizaeus-Merzbacher disease［J］.J Neurosci Res,2016,94(12):1572-1578.
［18］　JANG Y C,MUN B R,CHOI I S,et al.Rehabilitative management of an infant with Pelizaeus-Merzbacher disease:a case report［J］.Medicine (Baltimore),2020,99(22):e20110.
［19］　JI H,LI D,WU Y,et al.Hypomyelinating disorders in China:the clinical and genetic heterogeneity in 119 patients［J］.PLoS One,2018,13(2):e188869.
［20］　SARRET C,LEMAIRE J J,TONDUTI D,et al.Time-course of myelination and atrophy on cerebral imaging in 35 patients with PLP1-related disorders［J］.Dev Med Child Neurol,2016,58(7):706-713.
［21］　YAMAMOTO-SHIMOJIMA K,AKAGAWA H,YANAGI K,et al.Deep intronic deletion in intron 3 of PLP1 is associated with a severe phenotype of Pelizaeus-Merzbacher disease［J］.Hum Genome Var,2021,8(1):14.
［22］　穆卫红,侯晓琳,王思雯,等.一个佩梅病大家系的蛋白脂蛋白1基因的变异分析［J］.中华医学遗传学杂志,2019,36(12):1235-1237.
MU W H,HOU X L,WANG S W,et al.Variation analysis of the proteolipid protein 1 gene in a family with Pelizaeus-Merzbacher disease［J］.Chin J Med Genet,2019,36(12):1235-1237.
［23］　GROSSI S,REGIS S,BIANCHERI R,et al.Molecular genetic analysis of the PLP1 gene in 38 families with PLP1-related disorders:identification and functional characterization of 11 novel PLP1 mutations［J］.Orphanet J Rare Dis,2011,6:40.
［24］　HBNER C A,ORTH U,SENNING A,et al.Seventeen novel PLP1 mutations in patients with Pelizaeus-Merzbacher disease［J］.Hum Mutat,2005,25(3):321-322.

相似文献/References:

[1]武莉萍,杨留勤,张巍巍.鼻咽癌85例临床特征分析[J].新乡医学院学报,2002,19(04):318.
[2]孙秀利,王瑜.卵巢破裂62例临床分析[J].新乡医学院学报,2003,20(06):434.
[3]董　琳.2岁以下儿童支原体肺炎临床特征分析[J].新乡医学院学报,2017,34(6):517.[doi:10.7683/xxyxyxb.2017.06.017]
　DONG Lin.Clinical characteristics of mycoplasma pneumoniae pneumonia in children under two years old[J].Journal of Xinxiang Medical University,2017,34(2):517.[doi:10.7683/xxyxyxb.2017.06.017]
[4]张景航,薛　云,王冠男,等.幼年性黄色肉芽肿13例病理学分析[J].新乡医学院学报,2021,38(1):048.[doi:10.7683/xxyxyxb.2021.01.010]
　ZHANG Jinghang,XUE Yun,WANG Guannan,et al.Pathological analysis of 13 cases of juvenile xanthogranuloma[J].Journal of Xinxiang Medical University,2021,38(2):048.[doi:10.7683/xxyxyxb.2021.01.010]
[5]郭新珍.侵袭性肺炎克雷伯菌肝脓肿综合征患者临床特征分析[J].新乡医学院学报,2018,35(6):525.[doi:10.7683/xxyxyxb.2018.06.019]
　GUO Xin-zhen.Analysis of the clinical features on invasive Klebsiella pneumoniae liver abscess syndrome[J].Journal of Xinxiang Medical University,2018,35(2):525.[doi:10.7683/xxyxyxb.2018.06.019]
[6]谢　娜,邓建中,齐进兴,等.基于形态学病因分类的3种类型急性孤立性脑桥梗死的临床特征、影像学特征及预后比较[J].新乡医学院学报,2022,39(2):141.[doi:10.7683/xxyxyxb.2022.02.008]
　XIE Na,DENG Jianzhong,QI Jinxing,et al.Comparison of clinical features,imaging features and prognosis of three types of acute isolated pontine infarction based on morphological etiological classification[J].Journal of Xinxiang Medical University,2022,39(2):141.[doi:10.7683/xxyxyxb.2022.02.008]
[7]阎　磊,范晓光,高素华,等.肾组织M-型磷脂酶A2受体抗原阳性的特发性膜性肾病患者临床特征分析[J].新乡医学院学报,2017,34(8):700.[doi:10.7683/xxyxyxb.2017.08.010]
　YAN Lei,FAN Xiao-guang,GAO Su-hua,et al.Clinical features of patients with kidney tissue M-type phospholipase A2 receptor antigen positive idiopathic membranous nephropathy[J].Journal of Xinxiang Medical University,2017,34(2):700.[doi:10.7683/xxyxyxb.2017.08.010]
[8]谢二娟.泪小管裂伤研究进展[J].新乡医学院学报,2016,33(4):336.[doi:10.7683/xxyxyxb.2016.04.023]
　XIE Erjuan.Research progress of laceration of lacrimal canaliculus[J].Journal of Xinxiang Medical University,2016,33(2):336.[doi:10.7683/xxyxyxb.2016.04.023]
[9]薛　红,刘一村,程苕莼,等.瘦型与肥胖型代谢相关脂肪性肝病患者的临床特征比较[J].新乡医学院学报,2022,39(8):731.[doi:10.7683/xxyxyxb.2022.08.006]
　XUE Hong,LIU Yicun,CHEN Tiaochun,et al.Comparison of clinical characteristics of lean and obese patients with metabolic associated fatty liver disease[J].Journal of Xinxiang Medical University,2022,39(2):731.[doi:10.7683/xxyxyxb.2022.08.006]
[10]王元元,赵明理,刘素晓,等.恶性肺结节110例临床和影像学特征与病理类型的相关性分析[J].新乡医学院学报,2023,40(4):343.[doi:10.7683/xxyxyxb.2023.04.009]
　WANG Yuanyuan,ZHAO Mingli,LIU Suxiao,et al.Correlation analysis of clinical and imaging features and pathological types in 110 patients with malignant pulmonary nodules[J].Journal of Xinxiang Medical University,2023,40(2):343.[doi:10.7683/xxyxyxb.2023.04.009]

更新日期/Last Update: 2022-02-05