Genetic and Prenatal Diagnosis Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
BMC Med Genomics. 2021 Mar 23;14(1):88. doi: 10.1186/s12920-021-00940-z.
Distal 8p duplication is rare but clinically significant. Duplication syndrome results in variable phenotypes, such as developmental delay, intellectual disability, and malformation of the heart. We aimed to provide a better understanding of the phenotypes by studying duplication and its effects in a single family.
In a family with a previously induced labor (second fetus) at 12 weeks gestation due to increased nuchal translucency (3.5 mm), copy number variation sequencing (CNV-seq) revealed a 16.22 Mb deletion of 8p23.3p22. For their subsequent pregnancy, the family requested a prenatal diagnosis as well as CNV-seq, karyotyping and FISH testing of all family members.
The first and third children were found to have a 16.22 Mb duplication of 8p23.3p22, containing the 8p23.1 duplication syndrome region. The duplication was inherited from their father, a carrier with a translocation of 8p22 and 22q13. We confirmed that the duplication site was located on chromosome 22q13 by combining the results of CNV-seq, karyotype and FISH. The first child is a 7.5-year-old boy. At one month old, he was diagnosed with a ventricular septal defect and treated surgically at age four. His growth and intelligence developed well, and he performed well in school. His primary issue is an inability to distinguish between the blade alveolars and retroflexes in speech. The third fetus had a normal ultrasound index from beginning until birth. The family elected to continue the pregnancy, and the baby was born healthy, providing us the opportunity to evaluate the effects of 8p23.3p22 duplication by comparison with the brother.
Our study makes a significant contribution to the literature because this relatively rare condition can have significant phenotypical consequences, and an understanding of the inheritance and variability of phenotypes caused by this mutation is essential to an increased understanding of the condition.
远端 8p 重复极为罕见，但具有重要的临床意义。重复综合征导致多种表型，如发育迟缓、智力障碍和心脏畸形。我们旨在通过研究单个家庭中的重复及其影响，来更好地了解这些表型。
在一个家庭中，由于颈项透明层（3.5mm）增加，在 12 周妊娠时进行了引产（第二胎）。随后对该家庭进行了拷贝数变异测序（CNV-seq），结果显示 8p23.3p22 存在 16.22Mb 的缺失。对于他们的后续妊娠，该家庭要求进行产前诊断以及 CNV-seq、核型分析和所有家庭成员的 FISH 检测。
第一个和第三个孩子被发现携带 8p23.3p22 的 16.22Mb 重复，包含 8p23.1 重复综合征区域。该重复是从其父亲那里遗传的，父亲是一位携带者，发生了 8p22 和 22q13 的易位。我们通过结合 CNV-seq、核型和 FISH 的结果，证实了重复的位置位于 22q13 染色体上。第一个孩子是一个 7.5 岁的男孩。在一个月大时，他被诊断出患有室间隔缺损，并在四岁时接受了手术治疗。他的生长和智力发育良好，在学校表现出色。他的主要问题是在说话时无法区分齿龈音和卷舌音。第三个胎儿的超声指标从开始到出生一直正常。该家庭选择继续妊娠，孩子出生健康，这使我们有机会通过与哥哥进行比较来评估 8p23.3p22 重复的影响。
我们的研究对文献做出了重要贡献，因为这种相对罕见的情况可能会产生显著的表型后果，了解这种突变引起的遗传和表型变异性对于增加对该疾病的认识至关重要。
