与RNU4-2变异相关的ReNU综合征病例系列的基因型-表型相关性和表型扩展

IF 3.7 2区 医学 Q2 GENETICS & HEREDITY
Yukiko Kuroda, Koki Nagai, Yasuhiro Kawai, Takuya Naruto, Harutaka Saijou, Shotaro Morikawa, Tomohide Goto, Mutsumi Sato, Kenji Kurosawa
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引用次数: 0

摘要

RNU4-2编码U4小核RNA (snRNA),这是一种通过U4/U6 snRNA双工形成剪接体复合物的非编码RNA。RNU4-2杂合变异体引起ReNU综合征,以智力残疾、发育迟缓、癫痫、身材矮小和明显的畸形特征为特征。ReNU综合征占所有发育迟缓病例的0.4-0.5%,RNU4-2变异位于U4 snRNA的t环或干III区,其中约80%为t环内的n.64_65insT变异。我们从93名发育迟缓的个体中发现了4名日本患者(4.3%)患有新型和复发性RNU4-2变异,外显子组测序结果为阴性。在本病例系列和文献综述中观察到基因型-表型相关性。T-loop变异表现出严重的发育迟缓,超过70%的病例是非语言的。Stem III区域变异导致轻度发育迟缓,言语流利,大肌肉运动发育接近正常。此外,我们报告了一名顽固性癫痫患者,其神经功能减退,携带一种新的杂合RNU4-2变异(n.66A>G)。本报告扩展了ReNU综合征的表型谱,并提示存在与变异位置相关的表型变异性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Genotype-phenotype correlations and phenotypic expansion in a case series of ReNU syndrome associated with RNU4-2 variants.

RNU4-2 encodes U4 small nuclear RNA (snRNA), a non-coding RNA forming the spliceosome complex via the U4/U6 snRNA duplex. RNU4-2 heterozygous variants cause ReNU syndrome, which is characterised by intellectual disability, developmental delay, epilepsy, short stature and distinctive dysmorphic features. ReNU syndrome accounts for 0.4-0.5% of all cases of developmental delay, and RNU4-2 variants are located in the T-loop or stem III region of U4 snRNA, of which approximately 80% are the n.64_65insT variant in the T-loop. We identified four Japanese patients (4.3%) with novel and recurrent RNU4-2 variants from 93 individuals of developmental delay with negative results from exome sequencing. Genotype-phenotype correlations were observed in the present case series and a literature review. T-loop variants manifested severe developmental delay with more than 70% of cases being non-verbal. Stem III region variants resulted in milder developmental delay with fluent speech and nearly normal gross motor development milestones. In addition, we report a patient demonstrating intractable epilepsy with neurological regression harbouring a novel de novo heterozygous RNU4-2 variant (n.66A>G). This report expands the phenotypic spectrum of ReNU syndrome and suggests the presence of phenotypic variability related to variant location.

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来源期刊
Journal of Medical Genetics
Journal of Medical Genetics 医学-遗传学
CiteScore
7.60
自引率
2.50%
发文量
92
审稿时长
4-8 weeks
期刊介绍: Journal of Medical Genetics is a leading international peer-reviewed journal covering original research in human genetics, including reviews of and opinion on the latest developments. Articles cover the molecular basis of human disease including germline cancer genetics, clinical manifestations of genetic disorders, applications of molecular genetics to medical practice and the systematic evaluation of such applications worldwide.
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