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17p13.3微缺失/微重复与胎儿临床表型差异的遗传学分析——附五例报告
作者:杨滢1  朱湘玉1  王景美2  荆秀娟1  顾雷雷1  刘威1  王皖骏1  王亚平3  李洁1 
单位:1. 南京大学医学院附属南京鼓楼医院 妇产科, 江苏 南京 210008;
2. 南京大学医学院附属南京鼓楼医院 病理科, 江苏 南京 210008;
3. 南京大学医学院 医学遗传学研究室, 江苏 南京 210093
关键词:17p13.3微重复综合征 米勒· 迪克综合征 染色体微阵列分析 实时荧光定量聚合酶链反应 荧光原位杂交技术 
分类号:R596
出版年·卷·期(页码):2021·40·第四期(435-441)
摘要:

目的:探讨17p13.3区域微缺失/微重复胎儿遗传学异常与临床表型的关系。方法:应用染色体微阵列分析(CMA)方法检测5例胎儿样本的基因组拷贝数改变;采用实时荧光定量聚合酶链反应(q-PCR)检测技术及荧光原位杂交技术(FISH)检测判断胎儿17p13.3区域异常的亲本来源。结果:5例胎儿在染色体17p13.1-13.3区域存在不同程度的微缺失/微重复,病例1和病例4的17p13.3区域异常是新发突变,病例2和病例3为母源性,病例5的异常来源于染色体t (10;17)平衡易位的父亲。结论:基于17p13.3片段中所含关键基因的不同,病例1为17p13.3微重复综合征Ⅱ型,病例2为临床意义不明(VOUS),病例3、4和5均为17p13.3区域DNA拷贝数异常关联的米勒·迪克综合征(MDS),病例3的母亲也为MDS。17p13.3区域微缺失/微重复综合征患儿表型的严重程度与其异常的DNA片段所含有的关键基因直接相关。

Objective: To investigate the relationship between genetic abnormalities and fetal phenotypes in 17p13.3 region. Methods: Five fetal samples were detected by chromosome microarray analysis(CMA), and the parental origin of 17p13.3 abnormalities in fetus was determined by real-time quantitative polymerase chain reaction(q-PCR) and metaphase fluorescence in situ hybridization(FISH). Results: There were microdeletions/microduplications in chromosome 17p13.3 in these 5 fetuses. 17p13.3 abnormalities in fetus 1 and 4 were de novo, in fetus 2 and 3 were maternal and in fetus 5 were originated from the father with t(7;10). Conclusion: According to the different key genes contained in 17p13.3, fetus 1 is a patient with 17p13.3 microduplication syndrome type Ⅱ, fetus 2 is variants of unknown significance(VOUS), fetus 3,4 and 5 are patients with Miller-Dieker syndrome(MDS), and the mother of fetus 3 is also a MDS patient. Fetal phenotype of 17p13.3 microdeletion/microduplication is directly related with the key genes involved in abnormalities.

参考文献:

[1] CARDOSO C, LEVENTER R J, WARD H L, et al. Refinement of a 400-kb critical region allows genotypic differentiation between isolated lissencephaly, Miller-Dieker syndrome, and other phenotypes secondary to deletions of 17p13.3[J]. Am J Hum Genet, 2003, 72:918-930.
[2] NAGAMANI S C, ZHANG F, SHCHELOCHKOV O A, et al. Microdeletions including YWHAE in the Miller-Dieker syndrome region on chromosome 17p13.3 result in facial dysmorphisms, growth restriction, and cognitive impairment[J]. J Med Genet, 2009, 46:825-833.
[3] TAKAHASHI S, TANAKA R, OKANO S, et al. Characterization of intragenic tandem duplication in the PAFAH1B1 gene leading to isolated lissencephaly sequence[J]. Mol Cytogenet, 2015, 8:84-89.
[4] BI W, SAPIR T, SHCHELOCHKOV O A, et al. Increased LIS1 expression affects human and mouse brain development[J]. Nat Genet, 2009, 41:168-177.
[5] BRUNO D L, ANDERLID B M, LINDSTRAND A, et al. Further molecular and clinical delineation of co-locating 17p13.3 microdeletions and microduplications that show distinctive phenotypes[J]. J Med Genet, 2010, 47:299-311.
[6] CURRY C J, ROSENFELD J A, GRANT E, et al. The duplication 17p13.3 phenotype:analysis of 21 families delineates developmental, behavioral and brain abnormalities, and rare variant phenotypes[J]. Am J Med Genet A, 2013, 161A(8):1833-1852.
[7] STANKIEWICZ P, SHAW C J, DAPPER J D, et al. Genome architecture catalyzes nonrecurrent chromosomal rearrangements[J]. Am J Hum Genet, 2003, 72:1101-1116.
[8] KOMOIKE Y, SHIMOJIMA K, LIANG J S, et al. A functional analysis of GABARAP on 17p13.1 by knockdown zebrafish[J]. J Hum Genet, 2010, 55:155-162.
[9] SHIMOJIMA K, SUGIURA C, TAKAHASHI H, et al. Genomic copy number variations at 17p13.3 and epileptogenesis[J]. Epilepsy Res, 2010, 89:303-309.
[10] DITTWALD P, GAMBIN T, SZAFRANSKI P, et al. NAHR-mediated copy-number variants in a clinical population:mechanistic insights into both genomic disorders and Mendelizing traits[J]. Genome Res, 2013, 23(9):1395-1409.
[11] DE SMAELE E, DI MARCOTULLIO L, FERRETTI E, et al. Chromosome 17p deletion in human medulloblastoma:a missing checkpoint in the Hedgehog pathway[J]. Cell Cycle, 2004, 3:1263-1266.
[12] SCHNAITER A, STILGENBAUER S.17p deletion in chronic lymphocytic leukemia:risk stratification and therapeutic approach[J]. Hematol Oncol Clin North Am, 2013, 27:289-301.
[13] GAZZELLONE M J, ZHOU X, LIONEL A C, et al. Copy number variation in Han Chinese individuals with autism spectrum disorder[J]. J Neurodev Disord, 2014, 6:34-40.
[14] BLAZEJEWSKI S M, BENNISON S A, SMITH T H, et al. Neurodevelopmental genetic diseases associated with microdeletions and microduplications of chromosome 17p13.3[J]. Front Genet, 2018, 9:80-97.
[15] TENNEY J R, HOPKIN R J, SCHAPIRO M B.Deletion of 14-3-3{varepsilon} and CRK:a clinical syndrome with macrocephaly, developmental delay, and generalized epilepsy[J]. J Child Neurol, 2011, 26:223-227.
[16] 杨滢, 朱瑞芳, 朱湘玉, 等.一例涉及17p13.3微缺失患儿家系的临床表型、遗传学分析及产前诊断[J]. 中华围产医学杂志, 2017, 20(6):414-419.
[17] BARROS-FONTES M I, DOS SANTOS A P, ROSSI-TORRES F, et al. 17p13.3 microdeletion:insights on genotype-phenotype correlation[J]. Mol Syndromol, 2017, 8:36-41.
[18] SCHIFF M, DELAHAYE A, ANDRIEUX J, et al. Further delineation of the 17p13.3 microdeletion involving YWHAE but distal to PAFAH1B1:four additional patients[J]. Eur J MedGenet, 2010, 53(5):303-308.
[19] CANDELO E, CAICEDO G, MEJIA L, et al. Chromosome 17p13.3 microdeletion syndrome with unaltered PAFAH1B1 gene[J]. Neurologia, 2019, 34(7):482-484.
[20] CHEN C P, KO T M, WANG L K, et al. Prenatal diagnosis of a 0.7-Mb 17p13.3 microdeletion encompassing YWHAE and CRK but not PAFAH1B1 in a fetus without ultrasound abnormalities[J]. Taiwan J Obstet Gynecol, 2018, 57(1):128-132.
[21] HIRASAWA-INOUE A, TAKESHITA E, SHIMIZU-MOTOHASHI Y, et al. Static leukoencephalopathy associated with 17p13.3 microdeletion syndrome:a case report[J]. Neuropediatrics, 2019, 50(6):387-390.
[22] ROMANO C, FERRANTI S, MENCARELLI M A, et al. 17p13.3 microdeletion including YWHAE and CRK genes:towards a clinical characterization[J]. Neurol Sci, 2020, 41(8):2259-2262.
[23] 党颖慧, 万陕宁, 宋婷婷, 等.产前诊断5例17p13.3微缺失/微重复综合征[J]. 山西医科大学学报, 2020, 51(11):1268-1272.
[24] JOYCE C A, DENNIS N R, HOWARD F, et al. An 11p;17p telomeric translocation in two families associated with recurrent miscarriages and Miller-Dieker syndrome[J]. Eur J Hum Genet, 2002, 10(11):707-714.
[25] POLLIN T I, DOBYNS W B, CROWE C A, et al. Risk of abnormal pregnancy outcome in carriers of balanced reciprocal translocations involving the Miller-Dieker syndrome(MDS) critical region in chromosome 17p13.3[J]. Am J Med Genet, 1999, 85(4):369-375.
[26] ALVARDO M, BASS H N, CALDWELL S, et al. Miller-Dieker syndrome.Detection of a cryptic chromosome translocation using in situ hybridization in a family with multiple affected offspring[J]. Am J Dis Child, 1993, 147(12):1291-1294.
[27] BERRY R, WILSON H, ROBINSON J, et al. Apparent Smith-Lemli-Opitz syndrome and Miller-Dieker syndrome in a family with segregating translocation t(7;17)(q34;p13.1)[J]. Am J Med Genet, 1989, 34(3):358-365.
[28] KWON Y T, KASHINA A S, DAVYDOV I V, et al. An essential role of N-terminal arginylation in cardiovascular development[J]. Science, 2002, 297:96-99.

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