Prenatal exome sequencing in anomalous fetuses: new opportunities and challenges.
Prenatal exome sequencing in anomalous fetuses: new opportunities and challenges.
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DOI：
10.1038/gim.2017.33
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发表时间：
2017-11
期刊：
影响因子：
--
通讯作者：
Evans JP
中科院分区：
文献类型：
--
作者：
Vora NL;Powell B;Brandt A;Strande N;Hardisty E;Gilmore K;Foreman AKM;Wilhelmsen K;Bizon C;Reilly J;Owen P;Powell CM;Skinner D;Rini C;Lyerly AD;Boggess KA;Weck K;Berg JS;Evans JP
我们研究了外显子组测序(ES)在具有正常核型、微阵列和某些情况下正常基因特异性测序的超声异常胎儿中的诊断和临床表现。对15例畸形胎儿及其父母的外周血行ES。父母同意返回胎儿的诊断结果，父母的医学发现可采取行动，并确认为重大常染色体隐性遗传疾病的携带者夫妇。我们用混合方法评估了15个父母亲对ES的认知和理解。在15个胎儿中的7个(47%)，ES通过鉴定以下基因的变异来提供诊断或可能的诊断：COL1A1、穆斯克、KCTD1、RTTN、TMEM67、PIEZO1和DYNC2H1。另一例发现了一种新的候选基因(MAP4K4)的从头无义突变。ES解释结果的感知可能性(5.2/10)高于测试前咨询中讨论的约30%的诊断率。ES在高度怀疑基因诊断的高度精选的胎儿群体中具有诊断实用价值。与遗传学素养和变异解释相关的挑战必须通过高度量身定制的测试前和测试后遗传咨询来解决。
We investigated the diagnostic and clinical performance of exome sequencing (ES) in fetuses with sonographic abnormalities with normal karyotype, microarray and, in some cases, normal gene specific sequencing. ES was performed from DNA of 15 anomalous fetuses and from peripheral blood from their parents. Parents provided consent for the return of diagnostic results in the fetus, medically actionable findings in the parents, and identification as carrier couple for significant autosomal recessive conditions. We assessed perceptions and understanding of ES with mixed-methods in 15 mother-father dyads. In 7 (47%) of 15 fetuses, ES provided a diagnosis or possible diagnosis with identification of variants in the following genes: COL1A1, MUSK, KCTD1, RTTN, TMEM67, PIEZO1; and DYNC2H1. One additional case revealed a de novo nonsense mutation in a novel candidate gene (MAP4K4). The perceived likelihood that ES would explain the results (5.2/10) was higher than the approximately 30% diagnostic yield discussed in pre-test counseling. ES has diagnostic utility in a highly select population of fetuses where a genetic diagnosis was highly suspected. Challenges related to genetics literacy, and variant interpretation must be addressed by highly tailored pre- and post-test genetic counseling.
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影响因子：
3.5
作者：
Kaphingst KA;Ivanovich J;Biesecker BB;Dresser R;Seo J;Dressler LG;Goodfellow PJ;Goodman MS
通讯作者：
Goodman MS
影响因子：
3.7
作者：
Jung CH;Lee MJ;Kang YM;Yang DH;Kang JW;Kim EH;Park DW;Park JY;Kim HK;Lee WJ
通讯作者：
Lee WJ
影响因子：
6.2
作者：
Cukier HN;Dueker ND;Slifer SH;Lee JM;Whitehead PL;Lalanne E;Leyva N;Konidari I;Gentry RC;Hulme WF;Booven DV;Mayo V;Hofmann NK;Schmidt MA;Martin ER;Haines JL;Cuccaro ML;Gilbert JR;Pericak-Vance MA
通讯作者：
Pericak-Vance MA
DOI：
10.1038/gim.2013.73
发表时间：
2013-07
期刊：
Genetics in medicine : official journal of the American College of Medical Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
3
作者：
Shaffer, Lisa G.;Rosenfeld, Jill A.;Dabell, Mindy P.;Coppinger, Justine;Bandholz, Anne M.;Ellison, Jayw.;Ravnan, J. Britt;Torchia, Beth S.;Ballif, Blake C.;Fisher, Allan J.
通讯作者：
Fisher, Allan J.