Genetics and Molecular Biology, Laney Graduate School, Emory University, Atlanta, Georgia, USA.
Genetic Counseling Training Program, School of Medicine, Emory University, Atlanta, Georgia, USA.
Am J Med Genet A. 2020 May;182(5):1152-1166. doi: 10.1002/ajmg.a.61540. Epub 2020 Mar 10.
3q29 duplication syndrome (3q29dup) is a rare genomic disorder caused by a 1.6 Mb duplication (GRCh38 chr3:195,998,000-197,623,000). Case reports indicate the 3q29dup is likely to be pathogenic, but the full range of manifestations is not well understood. We used the 3q29 registry (https://3q29.com) to ascertain 31 individuals with 3q29dup, the largest cohort ever surveyed in a systematic way. For comparison, we ascertained 117 individuals with the reciprocal 3q29 deletion and 64 typically developing controls. We used a custom medical and demographic questionnaire to assess physical and developmental phenotypes, and two standardized instruments, the Social Responsiveness Scale and Child Behavior Checklist/Adult Behavior Checklist, to assess social disability. Participants with 3q29dup report a high rate of problems in the first year of life (80.6%), including feeding problems (55%), failure to gain weight (42%), hypotonia (39%), and respiratory distress (29%). In early childhood, learning problems (71.0%) and seizures (25.8%) are common. Additionally, the rate of self-reported autism spectrum disorder diagnoses (39%) is substantially elevated compared to the general population, suggesting that the 3q29 duplication may be an autism susceptibility locus. This is the most comprehensive description of 3q29dup to date. Our findings can be used to develop evidence-based strategies for early intervention and management of 3q29dup.
3q29 重复综合征（3q29dup）是一种由 1.6Mb 重复引起的罕见基因组疾病（GRCh38 chr3：195,998,000-197,623,000）。病例报告表明 3q29dup 可能是致病性的，但完整的临床表现尚未完全了解。我们使用 3q29 登记处（https://3q29.com）确定了 31 名 3q29dup 患者，这是系统调查中最大的队列。作为比较，我们确定了 117 名具有相反的 3q29 缺失和 64 名正常发育对照者。我们使用定制的医疗和人口统计学问卷来评估身体和发育表型，以及两个标准化工具，即社会反应量表和儿童行为检查表/成人行为检查表，来评估社交障碍。3q29dup 患者报告在生命的第一年有很高的问题发生率（80.6%），包括喂养问题（55%）、体重不增（42%）、低张力（39%）和呼吸窘迫（29%）。在幼儿期，学习问题（71.0%）和癫痫发作（25.8%）很常见。此外，自我报告的自闭症谱系障碍诊断率（39%）与一般人群相比显著升高，这表明 3q29 重复可能是自闭症易感性位点。这是迄今为止对 3q29dup 的最全面描述。我们的研究结果可用于制定基于证据的早期干预和管理 3q29dup 的策略。
