Phenotypic shift in copy number variants: Evidence in 16p11.2 duplication syndrome.
Phenotypic shift in copy number variants: Evidence in 16p11.2 duplication syndrome.
复制标题
DOI：
10.1016/j.gim.2022.09.011
复制
发表时间：
2023-01
影响因子：
8.8
通讯作者：
Ledbetter, David H.
中科院分区：
文献类型：
--
作者：
Taylor, Cora M.;Finucane, Brenda M.;Moreno-De-Luca, Andres;Walsh, Lauren K.;Martin, Christa Lese;Ledbetter, David H.
复发性16p11.2重复产生广泛的临床结果，对认知和社会功能产生不同的影响。以家族为基础的拷贝数变异（CNV）研究揭示了基因组背景对变异表达率的重要贡献。在这项研究中，我们测量了16p11.2重复的表型影响，并量化了家庭背景对认知和社会结果的调节作用。基因组和临床资料，确定了41名先证者与16p11.2重复和他们的一级亲属。完成配对比较，以确定重复的预期与实际表现的标准化测试的智力（IQ）和社会功能（SRS-2）的影响。还计算了亲属和先证者之间的组内相关性（ICC）。与CNV阴性亲属相比，16p11.2重复的个体的认知和社会功能显着降低，而两组之间的ICC对于全量表IQ和SRS-2评分仍然很高。16p11.2重复对认知和社会功能产生有害影响，而家族背景显著影响这些特征的表型表达。了解CNV疾病中的可变表达性对预期的临床护理具有影响，特别是对于在早期接受遗传诊断的个体，远在表现的全部范围变得明显之前。
Recurrent 16p11.2 duplications produce a wide range of clinical outcomes with varying impacts on cognition and social functioning. Family-based studies of copy number variants (CNV) have revealed significant contributions of genomic background on variable expressivity. In this study, we measured the phenotypic impact of 16p11.2 duplications and quantified the modulating effect of familial background on cognitive and social outcomes. Genomic and clinical data were ascertained from 41 probands with a 16p11.2 duplication and their first-degree relatives. Paired comparisons were completed to determine the duplication’s impact on expected versus actual performance on standardized tests of intelligence (IQ) and social functioning (SRS-2). Intraclass correlations (ICCs) between relatives and probands were also calculated. Cognitive and social functioning were significantly lower among individuals with 16p11.2 duplications compared to their CNV-negative relatives, while ICCs between the groups remained high for full-scale IQ and SRS-2 scores. 16p11.2 duplications confer deleterious effects on cognition and social functioning, while familial background significantly influences phenotypic expression of these traits. Understanding variable expressivity in CNV disorders has implications for anticipatory clinical care, particularly for individuals who receive a genetic diagnosis at an early age, long before the full scope of manifestations becomes evident.
登录
查看更多内容
影响因子：
4
作者：
Chung, Wendy K.;Roberts, Timothy P. L.;Sherr, Elliott H.;Snyder, LeeAnne Green;Spiro, John E.
通讯作者：
Spiro, John E.
影响因子：
25.8
作者：
Moreno-De-Luca, Andres;Evans, David W.;Ledbetter, David H.
通讯作者：
Ledbetter, David H.
影响因子：
64.8
作者：
Jacquemont, Sebastien;Reymond, Alexandre;Froguel, Philippe
通讯作者：
Froguel, Philippe
影响因子：
3.1
作者：
Olszewski, Amy K.;Radoeva, Petya D.;Antshel, Kevin M.
通讯作者：
Antshel, Kevin M.
影响因子：
11
作者：
Cleynen, Isabelle;Engchuan, Worrawat;Bassett, Anne S.
通讯作者：
Bassett, Anne S.