Kagami Ogata syndrome: a small deletion refines critical region for imprinting.
Kagami Ogata syndrome: a small deletion refines critical region for imprinting.
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DOI：
10.1038/s41525-023-00389-2
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发表时间：
2024-01-11
影响因子：
5.3
通讯作者：
Sullivan, Kathleen E.
中科院分区：
文献类型：
--
作者：
Kilich, Gonench;Hassey, Kelly;Behrens, Edward M.;Falk, Marni;Vanderver, Adeline;Rader, Daniel J.;Cahill, Patrick J.;Raper, Anna;Zhang, Zhe;Westerfer, Dawn;Jadhav, Tanaya;Conlin, Laura;Izumi, Kosuke;Rajagopalan, Ramakrishnan;Sullivan, Kathleen E.
Kagami-Ogata综合征是一种罕见的印迹疾病，其表型重叠和多种不同的病因阻碍了诊断。遗传病因包括父本单亲等二体(UPD(14)PAT)、母体14q32.2差异甲基化区(DMR)等位基因缺失或纯原发突变。我们报告了一位患有Kagami-Ogata综合征的患者和一例非典型的诊断奥德赛，在几项阴性的护理标准基因测试之后，使用甲基化微阵列进行了表观遗传学测试，并对全基因组测序进行了有针对性的分析，发现了涉及meg3转录本和meg3：tss-dmr的203 碱基缺失。长阅读测序使得能够在一次检测中同时检测MEG3：TSS-DMR区域的缺失、定相和双等位基因高甲基化。这一案例突出了序列基因检测范例中的挑战，长读测序作为一种单一的综合诊断分析的实用性，以及已报道的导致Kagami-Ogata综合征的最小缺失，使人们能够对该基因座印记效应的机制进行重要的洞察。
Kagami–Ogata syndrome is a rare imprinting disorder and its phenotypic overlap with multiple different etiologies hampers diagnosis. Genetic etiologies include paternal uniparental isodisomy (upd(14)pat), maternal allele deletions of differentially methylated regions (DMR) in 14q32.2 or pure primary epimutations. We report a patient with Kagami–Ogata syndrome and an atypical diagnostic odyssey with several negative standard-of-care genetic tests followed by epigenetic testing using methylation microarray and a targeted analysis of whole-genome sequencing to reveal a 203 bp deletion involving the MEG3 transcript and MEG3:TSS-DMR. Long-read sequencing enabled the simultaneous detection of the deletion, phasing, and biallelic hypermethylation of the MEG3:TSS-DMR region in a single assay. This case highlights the challenges in the sequential genetic testing paradigm, the utility of long-read sequencing as a single comprehensive diagnostic assay, and the smallest reported deletion causing Kagami–Ogata syndrome allowing important insights into the mechanism of imprinting effects at this locus.
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DOI：
10.1038/gim.2017.53
发表时间：
2017-12
期刊：
Genetics in medicine : official journal of the American College of Medical Genetics
影响因子：
--
作者：
Kagami M;Nagasaki K;Kosaki R;Horikawa R;Naiki Y;Saitoh S;Tajima T;Yorifuji T;Numakura C;Mizuno S;Nakamura A;Matsubara K;Fukami M;Ogata T
通讯作者：
Ogata T
影响因子：
46.9
作者：
Poplin, Ryan;Chang, Pi-Chuan;DePristo, Mark A.
通讯作者：
DePristo, Mark A.
影响因子：
8.8
作者：
Sanli, Ildem;Lalevee, Sebastien;Feil, Robert
通讯作者：
Feil, Robert
影响因子：
0.9
作者：
Sakaria RP;Mostafavi R;Miller S;Ward JC;Pivnick EK;Talati AJ
通讯作者：
Talati AJ
影响因子：
30.8
作者：
Ohm, Joyce E.;McGarvey, Kelly M.;Baylin, Stephen B.
通讯作者：
Baylin, Stephen B.