Goh Shuxiang, Thiyagarajan Lavvina, Dudding-Byth Tracy, Pinese Mark, Kirk Edwin P
School of Clinical Medicine, University of New South Wales, Sydney, NSW, Australia; New South Wales Health, NSW, Australia.
School of Clinical Medicine, University of New South Wales, Sydney, NSW, Australia; New South Wales Health, NSW, Australia; The Children's Hospital at Westmead, Sydney, NSW, Australia.
Genet Med. 2025 Jan;27(1):101227. doi: 10.1016/j.gim.2024.101227. Epub 2024 Jul 30.
Many copy-number variants (CNVs) are reported to cause a variety of neurodevelopmental disabilities including intellectual disability, developmental delay, autism, and other phenotypes with incomplete penetrance. Therefore, not all individuals with a pathogenic CNV are affected. Penetrance estimates vary between studies. A systematic review was conducted to clarify CNV penetrance for 83 recurrent CNVs.
A systematic review using PRISMA guidelines (PROSPERO #CRD42021253955) was conducted to identify penetrance estimates for CNVs associated with neurodevelopment. Pooled analysis was performed using forest plots. The Ottawa Risk of Bias Assessment facilitated evaluation.
Fifteen studies were reviewed in detail with 9 affected cohorts pooled and compared with the gnomAD v4.0 CNV control cohort of 269,885 individuals. Several CNVs previously associated with nonstatistically significant penetrance estimates now exhibit statistically significant differences, contributing to emerging evidence for their pathogenicity (15q24 duplication [A-D breakpoints], 15q24.2q24.5 deletion and duplication [FBXO22], 17q11.2 duplication [NF1], 17q21.31 duplication [KANSL1] and 22q11.2 distal duplication). Additionally, evidence is presented for the benign nature of some CNVs (15q11.2 duplication [NIPA1] and 2q13 proximal duplication [NPHP1]).
This is a large-scale systematic review of CNVs associated with neurodevelopment. A synopsis analyzing penetrance and pathogenicity is provided for each of the 83 recurrent CNVs.
据报道，许多拷贝数变异（CNV）会导致多种神经发育障碍，包括智力残疾、发育迟缓、自闭症以及其他外显不全的表型。因此，并非所有携带致病性CNV的个体都会受到影响。不同研究中的外显率估计有所不同。本研究进行了一项系统评价，以阐明83种复发性CNV的CNV外显率。
采用PRISMA指南（PROSPERO #CRD42021253955）进行系统评价，以确定与神经发育相关的CNV的外显率估计值。使用森林图进行汇总分析。渥太华偏倚风险评估有助于评估。
详细审查了15项研究，汇集了9个受影响队列，并与269,885名个体的gnomAD v4.0 CNV对照队列进行了比较。一些先前外显率估计无统计学意义的CNV，现在显示出统计学上的显著差异，为其致病性提供了新的证据（15q24重复[A-D断点]、15q24.2q24.5缺失和重复[FBXO22]、17q11.2重复[NF1]、17q21.31重复[KANSL1]和22q11.2远端重复）。此外，还提供了一些CNV（15q11.2重复[NIPA1]和2q13近端重复[NPHP1]）具有良性性质的证据。
这是一项关于与神经发育相关的CNV的大规模系统评价。为83种复发性CNV中的每一种提供了一份分析外显率和致病性的综述。
