Refining the Phenotypic Spectrum of KMT5B-Associated Developmental Delay.
Refining the Phenotypic Spectrum of KMT5B-Associated Developmental Delay.
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完善 KMT5B 相关发育迟缓的表型光谱
DOI：
10.3389/fped.2022.844845
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发表时间：
2022
影响因子：
2.6
通讯作者：
中科院分区：
文献类型：
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作者：
赖氨酸甲基转移酶 (KMT) 和去甲基酶 (KDM) 在染色质修饰调节中的作用已明确。最近，KMT5B 中的有害杂合变异与智力障碍 (ID) 和/或自闭症谱系障碍患者有关。我们描述了三名不相关的患有整体发育迟缓（GDD）或智力障碍、大头畸形和其他特征的患者。使用全外显子组测序，发现每个先证者在 KMT5B 中都含有独特的从头杂合致病变异：c.541C > G (p.His181Asp)； c.833A > T (p.Asn278Ile)；或c.391_394delAAAG（p.Lys131GlufsTer6）。我们在此讨论他们的临床表现，并将其与之前报告的患者进行比较。此外，使用 KMT5B 蛋白的三维计算模型，我们证明了两种错义变体的预测结构效应。我们的研究结果支持新的错义和无义变异在 KMT5B 相关 GDD/ID 中的作用，并表明在伴有大头畸形和/或过度生长的神经发育障碍的鉴别诊断中应考虑该基因。
The role of lysine methyltransferases (KMTs) and demethylases (KDMs) in the regulation of chromatin modification is well-established. Recently, deleterious heterozygous variants in KMT5B were implicated in individuals with intellectual disability (ID) and/or autism spectrum disorder. We describe three unrelated patients with global developmental delay (GDD) or ID, macrocephaly and additional features. Using whole exome sequencing, each of the probands was found to harbor a distinct de novo heterozygous disease-causing variant in KMT5B: c.541C > G (p.His181Asp); c.833A > T (p.Asn278Ile); or c.391_394delAAAG (p.Lys131GlufsTer6). We discuss herein their clinical presentations, and compare them to those of previously reported patients. Furthermore, using a three-dimensional computational model of the KMT5B protein, we demonstrate the predicted structural effects of the two missense variants. Our findings support the role of de novo missense and nonsense variants in KMT5B-associated GDD/ID, and suggest that this gene should be considered in the differential diagnosis of neurodevelopmental disorders accompanied by macrocephaly and/or overgrowth.
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影响因子：
4.6
作者：
Pode-Shakked B;Barel O;Singer A;Regev M;Poran H;Eliyahu A;Finezilber Y;Segev M;Berkenstadt M;Yonath H;Reznik-Wolf H;Gazit Y;Chorin O;Heimer G;Gabis LV;Tzadok M;Nissenkorn A;Bar-Yosef O;Zohar-Dayan E;Ben-Zeev B;Mor N;Kol N;Nayshool O;Shimshoviz N;Bar-Joseph I;Marek-Yagel D;Javasky E;Einy R;Gal M;Grinshpun-Cohen J;Shohat M;Dominissini D;Raas-Rothschild A;Rechavi G;Pras E;Greenbaum L
通讯作者：
Greenbaum L
影响因子：
64.8
作者：
Iossifov, Ivan;O'Roak, Brian J.;Sanders, Stephan J.;Ronemus, Michael;Krumm, Niklas;Levy, Dan;Stessman, Holly A.;Witherspoon, Kali T.;Vives, Laura;Patterson, Karynne E.;Smith, Joshua D.;Paeper, Bryan;Nickerson, Deborah A.;Dea, Jeanselle;Dong, Shan;Gonzalez, Luis E.;Mandell, Jeffrey D.;Mane, Shrikant M.;Murtha, Michael T.;Sullivan, Catherine A.;Walker, Michael F.;Waqar, Zainulabedin;Wei, Liping;Willsey, A. Jeremy;Yamrom, Boris;Lee, Yoon-ha;Grabowska, Ewa;Dalkic, Ertugrul;Wang, Zihua;Marks, Steven;Andrews, Peter;Leotta, Anthony;Kendall, Jude;Hakker, Inessa;Rosenbaum, Julie;Ma, Beicong;Rodgers, Linda;Troge, Jennifer;Narzisi, Giuseppe;Yoon, Seungtai;Schatz, Michael C.;Ye, Kenny;McCombie, W. Richard;Shendure, Jay;Eichler, Evan E.;State, Matthew W.;Wigler, Michael
通讯作者：
Wigler, Michael
影响因子：
12.3
作者：
Dillon SC;Zhang X;Trievel RC;Cheng X
通讯作者：
Cheng X
影响因子：
14.9
作者：
Waterhouse A;Bertoni M;Bienert S;Studer G;Tauriello G;Gumienny R;Heer FT;de Beer TAP;Rempfer C;Bordoli L;Lepore R;Schwede T
通讯作者：
Schwede T
DOI：
10.1038/nrg3173
发表时间：
2012-04-03
期刊：
Nature reviews. Genetics
影响因子：
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作者：
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