{"title":"“42个种系PALB2剪接位点变异的剪接预测、小基因分析和ACMG-AMP临床分类”","authors":"","doi":"10.1002/path.6215","DOIUrl":null,"url":null,"abstract":"<p>By Alberto Valenzuela-Palomo, Elena Bueno-Martínez, Lara Sanoguera-Miralles, Víctor Lorca, Eugenia Fraile-Bethencourt, Ada Esteban-Sánchez, Susana Gómez-Barrero, Sara Carvalho, Jamie Allen, Alicia García-Álvarez, Pedro Pérez-Segura, Leila Dorling, Douglas F Easton, Peter Devilee, Maaike PG Vreeswijk, Miguel de la Hoya<sup>†</sup> and Eladio A Velasco<sup>†</sup>, <i>J Pathol</i> 2022; <b>256:</b> 321–334. https://doi.org/10.1002/path.5839. <sup>†</sup>Senior authors.</p><p>The senior authors of this article, first published on 30 November 2021 in Wiley Online Library (wileyonlinelibrary.com), have informed the editors of an unintentional mistake that they wish to correct, and they explain why below.</p><p>In our manuscript, we described minigene splicing read-outs for 42 <i>PALB2</i> variants. Two of them, c.1685-2A>C and c.1685-2A>G (acceptor site of exon 5), displayed a complex pattern of five anomalous transcripts: ∆(E5p139), ∆(E5p5), ▼(E5p88), ∆(E5p10) and ∆(E5p97) (Table 1 and Figure 2B of the original manuscript).</p><p>Therefore, Δ(E5p510) represents roughly 18% and 25% of the overall minigene expression of c.1685-2A>C and c.1685-2A>G, respectively.</p><p>In the light of our new data, we re-evaluated the ACMG-AMP point-based system classification of both variants.</p><p>Since all the initially minigene-detected transcripts were PTC_NMD (∆(E5p139), ▼(E5p88), ∆(E5p10), ∆(E5p97) and ∆(E5p5)), we had previously assigned PS3_VS (+8) to both variants (supplementary material, Table S2, and Table 2). Yet, ∆(E5p510) makes a substantial contribution to the overall expression. Moreover, this transcript encodes for an in-frame protein deletion, p.(Lys563_Gly732del), which removes >10% of the protein sequence but does not target known critical PALB2 domains, so that ∆(E5p510) finally qualifies for a PS3 code.</p><p><b>Figure C1.</b> Fluorescent fragment analysis of the wild type minigene mgPALB2_ex4-6 and variants c.1685-2A>C and c.1685-2A>G. FAM-labeled products (blue peaks) were run with LIZ-1200 (orange peaks) as size standards. The <i>x</i>-axis indicates size in bp (electropherogram on the top) and the <i>y</i>-axis represents relative fluorescence units (RFU). FL, minigene full-length transcript. As indicated in Materials and methods, cDNA was amplified with primers RTPB2_EX4-FW (5’-CACAAATATCAGCACGAAAA-3’) and FAM-RTPB2_EX6-RV (full-length size: 918 nt).</p><p>The authors apologise for any inconvenience this mistake may have caused.</p><p>The editors apologise for the time taken to process the request for this corrigendum and approve it.</p>","PeriodicalId":232,"journal":{"name":"The Journal of Pathology","volume":"261 3","pages":"372-373"},"PeriodicalIF":5.6000,"publicationDate":"2023-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/path.6215","citationCount":"1","resultStr":"{\"title\":\"‘Splicing predictions, minigene analyses, and ACMG-AMP clinical classification of 42 germline PALB2 splice-site variants’\",\"authors\":\"\",\"doi\":\"10.1002/path.6215\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>By Alberto Valenzuela-Palomo, Elena Bueno-Martínez, Lara Sanoguera-Miralles, Víctor Lorca, Eugenia Fraile-Bethencourt, Ada Esteban-Sánchez, Susana Gómez-Barrero, Sara Carvalho, Jamie Allen, Alicia García-Álvarez, Pedro Pérez-Segura, Leila Dorling, Douglas F Easton, Peter Devilee, Maaike PG Vreeswijk, Miguel de la Hoya<sup>†</sup> and Eladio A Velasco<sup>†</sup>, <i>J Pathol</i> 2022; <b>256:</b> 321–334. https://doi.org/10.1002/path.5839. <sup>†</sup>Senior authors.</p><p>The senior authors of this article, first published on 30 November 2021 in Wiley Online Library (wileyonlinelibrary.com), have informed the editors of an unintentional mistake that they wish to correct, and they explain why below.</p><p>In our manuscript, we described minigene splicing read-outs for 42 <i>PALB2</i> variants. Two of them, c.1685-2A>C and c.1685-2A>G (acceptor site of exon 5), displayed a complex pattern of five anomalous transcripts: ∆(E5p139), ∆(E5p5), ▼(E5p88), ∆(E5p10) and ∆(E5p97) (Table 1 and Figure 2B of the original manuscript).</p><p>Therefore, Δ(E5p510) represents roughly 18% and 25% of the overall minigene expression of c.1685-2A>C and c.1685-2A>G, respectively.</p><p>In the light of our new data, we re-evaluated the ACMG-AMP point-based system classification of both variants.</p><p>Since all the initially minigene-detected transcripts were PTC_NMD (∆(E5p139), ▼(E5p88), ∆(E5p10), ∆(E5p97) and ∆(E5p5)), we had previously assigned PS3_VS (+8) to both variants (supplementary material, Table S2, and Table 2). Yet, ∆(E5p510) makes a substantial contribution to the overall expression. Moreover, this transcript encodes for an in-frame protein deletion, p.(Lys563_Gly732del), which removes >10% of the protein sequence but does not target known critical PALB2 domains, so that ∆(E5p510) finally qualifies for a PS3 code.</p><p><b>Figure C1.</b> Fluorescent fragment analysis of the wild type minigene mgPALB2_ex4-6 and variants c.1685-2A>C and c.1685-2A>G. FAM-labeled products (blue peaks) were run with LIZ-1200 (orange peaks) as size standards. The <i>x</i>-axis indicates size in bp (electropherogram on the top) and the <i>y</i>-axis represents relative fluorescence units (RFU). FL, minigene full-length transcript. As indicated in Materials and methods, cDNA was amplified with primers RTPB2_EX4-FW (5’-CACAAATATCAGCACGAAAA-3’) and FAM-RTPB2_EX6-RV (full-length size: 918 nt).</p><p>The authors apologise for any inconvenience this mistake may have caused.</p><p>The editors apologise for the time taken to process the request for this corrigendum and approve it.</p>\",\"PeriodicalId\":232,\"journal\":{\"name\":\"The Journal of Pathology\",\"volume\":\"261 3\",\"pages\":\"372-373\"},\"PeriodicalIF\":5.6000,\"publicationDate\":\"2023-09-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1002/path.6215\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"The Journal of Pathology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/path.6215\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"The Journal of Pathology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/path.6215","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 1
摘要
Alberto Valenzuela Palomo、Elena Bueno Martínez、Lara Sanoguera Miralles、Víctor Lorca、Eugenia Fraile Bethencourt、Ada Esteban-Sánchez、Susana Gómez Barrero、Sara Carvalho、Jamie Allen、Alicia García-Álvarez、Pedro Pérez Segura、Leila Dorling、Douglas F Easton、Peter Devilee、Maaike PG Vreeswijk、Miguel de la Hoya†和Eladio a Velasco†，《病理学杂志》2022；256:321-334。https://doi.org/10.1002/path.5839.†资深作者。这篇文章于2021年11月30日首次发表在威利在线图书馆（wileyonlinelibrary.com），其资深作者已告知编辑他们希望纠正的一个无意错误，并在下面解释原因。在我们的手稿中，我们描述了42个PALB2变体的小基因剪接读数。其中两个，约1685-2A>；C和C.1685-2A>；G（外显子5的受体位点）显示出五种异常转录物的复杂模式：∆（E5p139）、∆，▼Δ（E5p510）约占c.1685-2A>；C和C.1685-2A>；G、 分别。根据我们的新数据，我们重新评估了两种变体的基于ACMG-AMP点的系统分类。由于最初检测到的所有小基因转录物都是PTC_ NMD（∆（E5p139），▼（E5p88）、∆（E5p10）、∆（E5p97）和∆（E6p5）），我们之前已将PS3_VS（+8）分配给这两种变体（补充材料，表S2和表2）。然而，∆（E5p510）对整体表达做出了重大贡献。此外，该转录物编码框内蛋白缺失p（Lys563_Gly732del），其去除>；10%的蛋白质序列，但不靶向已知的关键PALB2结构域，因此∆（E5p510）最终符合PS3编码。图C1。野生型小基因mgPALB2_ex4-6和变体c.1685-2A>；C和C.1685-2A>；G.FAM标记的产品（蓝色峰）以LIZ-1200（橙色峰）作为尺寸标准。x轴表示以bp为单位的大小（顶部的电泳图），y轴表示相对荧光单位（RFU）。FL，小基因全长转录物。如材料和方法所示，cDNA是用引物RTPB2_EX4-FW（5'-CAAATATCAGCACGAAAA-3'）和FAM-RTPB2_E6-RV（全长：918nt）扩增的。作者对这一错误可能造成的不便深表歉意。编辑们对处理和批准本更正请求所花费的时间表示歉意。
‘Splicing predictions, minigene analyses, and ACMG-AMP clinical classification of 42 germline PALB2 splice-site variants’
By Alberto Valenzuela-Palomo, Elena Bueno-Martínez, Lara Sanoguera-Miralles, Víctor Lorca, Eugenia Fraile-Bethencourt, Ada Esteban-Sánchez, Susana Gómez-Barrero, Sara Carvalho, Jamie Allen, Alicia García-Álvarez, Pedro Pérez-Segura, Leila Dorling, Douglas F Easton, Peter Devilee, Maaike PG Vreeswijk, Miguel de la Hoya† and Eladio A Velasco†, J Pathol 2022; 256: 321–334. https://doi.org/10.1002/path.5839. †Senior authors.
The senior authors of this article, first published on 30 November 2021 in Wiley Online Library (wileyonlinelibrary.com), have informed the editors of an unintentional mistake that they wish to correct, and they explain why below.
In our manuscript, we described minigene splicing read-outs for 42 PALB2 variants. Two of them, c.1685-2A>C and c.1685-2A>G (acceptor site of exon 5), displayed a complex pattern of five anomalous transcripts: ∆(E5p139), ∆(E5p5), ▼(E5p88), ∆(E5p10) and ∆(E5p97) (Table 1 and Figure 2B of the original manuscript).
Therefore, Δ(E5p510) represents roughly 18% and 25% of the overall minigene expression of c.1685-2A>C and c.1685-2A>G, respectively.
In the light of our new data, we re-evaluated the ACMG-AMP point-based system classification of both variants.
Since all the initially minigene-detected transcripts were PTC_NMD (∆(E5p139), ▼(E5p88), ∆(E5p10), ∆(E5p97) and ∆(E5p5)), we had previously assigned PS3_VS (+8) to both variants (supplementary material, Table S2, and Table 2). Yet, ∆(E5p510) makes a substantial contribution to the overall expression. Moreover, this transcript encodes for an in-frame protein deletion, p.(Lys563_Gly732del), which removes >10% of the protein sequence but does not target known critical PALB2 domains, so that ∆(E5p510) finally qualifies for a PS3 code.
Figure C1. Fluorescent fragment analysis of the wild type minigene mgPALB2_ex4-6 and variants c.1685-2A>C and c.1685-2A>G. FAM-labeled products (blue peaks) were run with LIZ-1200 (orange peaks) as size standards. The x-axis indicates size in bp (electropherogram on the top) and the y-axis represents relative fluorescence units (RFU). FL, minigene full-length transcript. As indicated in Materials and methods, cDNA was amplified with primers RTPB2_EX4-FW (5’-CACAAATATCAGCACGAAAA-3’) and FAM-RTPB2_EX6-RV (full-length size: 918 nt).
The authors apologise for any inconvenience this mistake may have caused.
The editors apologise for the time taken to process the request for this corrigendum and approve it.
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The Journal of Pathology aims to serve as a translational bridge between basic biomedical science and clinical medicine with particular emphasis on, but not restricted to, tissue based studies. The main interests of the Journal lie in publishing studies that further our understanding the pathophysiological and pathogenetic mechanisms of human disease.
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