Yang Xi, Hu Rong, Huang Weiwei, Lu Jian
Guangdong Provincial Research Center for Sports Assistive Device Design Engineering and Technology, Guangzhou Sport University, No.1268, Guangzhou Avenue Middle, Tianhe District, Guangzhou, 510500, Guangdong, People's Republic of China.
Medical Genetic Center, Guangdong Women and Children Hospital, NO.521-523, Xingnan Road, Panyu District, Guangzhou, Guangdong, 511442, People's Republic of China.
Orphanet J Rare Dis. 2025 Aug 11;20(1):421. doi: 10.1186/s13023-025-03969-w.
Inverted duplication of the short arm of chromosome 8 (inv dup del (8p)) and the deletion of its adjacent terminal represent a rare chromosomal rearrangement. To date, only a limited number of prenatal cases have been documented from a molecular cytogenetic perspective. This study investigates the molecular genetic characteristics and intrauterine ultrasound phenotypes of fetuses prenatally diagnosed with inv dup del (8p).
We retrospectively analyzed chromosomal microarray analysis (CMA) results from cases seeking prenatal diagnosis at the Medical Genetics Center of Guangdong Women and Children’s Hospital from January 2016 to December 2022. We identified 12 prenatal cases of inv dup del (8p) and summarized their prenatal clinical manifestations and associated genes by combining ultrasound findings with literature review.
Both G-banding and CMA techniques confirmed the presence of interstitial duplication with concomitant terminal deletion of chromosome 8’s short arm in all 12 cases. The locations and lengths of the 8p duplications varied in their proximal breakpoint. Observed ultrasound findings included fetal increased nuchal translucency (NT), lateral cerebral ventricular dilatation, craniofacial dysmorphisms and abnormalities of the brain, heart and kidneys. Ectopic recombination appears to be the dominant mechanism for rearrangement formation in cases 1–11. In contrast, case 12 exhibited inv dup del (8p) without an intact region between duplication and deletion, which is better explained by the U-type exchange mechanism.
The intrauterine phenotypes of inv dup del (8p) are diverse, with cerebral and cardiac anomalies being the most commonly observed ultrasound findings. However, these clinical manifestations are not specific to inv dup del (8p), and some fetuses may not exhibit noticeable ultrasound abnormalities during early gestation. Therefore, definitive diagnostic testing through karyotyping and CMA is essential. Additionally, CMA enables precise detection of copy number variations (CNVs), including exact size and genomic location. This detailed information is critical for accurate genetic counselling and helps clarify the mechanism behind the inv dup (8p) rearrangement.
The online version contains supplementary material available at 10.1186/s13023-025-03969-w.
8号染色体短臂的反向重复（inv dup del (8p)）及其相邻末端的缺失代表一种罕见的染色体重排。迄今为止，从分子细胞遗传学角度记录的产前病例数量有限。本研究调查产前诊断为inv dup del (8p)的胎儿的分子遗传特征和宫内超声表型。
我们回顾性分析了2016年1月至2022年12月在广东省妇幼保健院医学遗传中心进行产前诊断的病例的染色体微阵列分析（CMA）结果。我们确定了12例产前inv dup del (8p)病例，并通过结合超声检查结果和文献综述总结了它们的产前临床表现和相关基因。
G显带和CMA技术均证实所有12例病例均存在8号染色体短臂的间质重复并伴有末端缺失。8p重复的位置和长度在其近端断点处有所不同。观察到的超声检查结果包括胎儿颈项透明层（NT）增厚、侧脑室扩张、颅面畸形以及脑、心脏和肾脏异常。异位重组似乎是病例1至11中重排形成的主要机制。相比之下，病例12表现为inv dup del (8p)，重复和缺失之间没有完整区域，U型交换机制能更好地解释这一现象。
inv dup del (8p)的宫内表型多样，脑和心脏异常是最常见的超声检查结果。然而，这些临床表现并非inv dup del (8p)所特有，一些胎儿在妊娠早期可能未表现出明显的超声异常。因此，通过核型分析和CMA进行明确的诊断检测至关重要。此外，CMA能够精确检测拷贝数变异（CNV），包括确切大小和基因组位置。这些详细信息对于准确的遗传咨询至关重要，并有助于阐明inv dup (8p)重排背后的机制。
在线版本包含可在10.1186/s13023-025-03969-w获取的补充材料。
