Dataset Information

Detection of a rare de novo 18p terminal deletion with inverted duplication in a Chinese pregnant woman.

ABSTRACT:

Background

The 18p terminal deletion with inverted duplication is an extremely rare chromosome structure abnormality and the common clinical manifestations include intellectual disability and speech delay, etc. Up to now, only three confirmed cases were reported in Europe, and here, for the first time in the Asian population, we report a case of de novo 18p inv-dup-del in a Chinese pregnant woman. This structural variation was accidentally discovered by the noninvasive prenatal testing (NIPT) during her prenatal examination.

Methods

Next generation sequencing (NGS) based copy number variations (CNVs) screening and karyotype analysis were performed to verify the type and heredity of the rearrangement, and the fluorescent in situ hybridization (FISH) analysis was also used to confirm the terminal deletion and inverted duplication.

Results

The patient has a de novo 18p11.31-18p11.1 inverted duplication with a 6.2 Mb 18p terminal deletion. This rare chromosome imbalance, most likely caused by the U-type exchange mechanism, resulted in the aberrant phenotype of mental disability, speech delay, seizure, and strabismus. However, the rearrangement was not inherited by her unborn child.

Conclusion

This report added a new type of variation to the spectrum of 18p terminal deletion with inverted duplication, and demonstrated that the maternal chromosome rearrangement discovered in NIPT should not just be consider as an interference factor but also a potential indicator of previously undiscovered pathogenic chromosome structure variations in pregnant women.

SUBMITTER: Zhu J

PROVIDER: S-EPMC6732341 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Detection of a rare de novo 18p terminal deletion with inverted duplication in a Chinese pregnant woman.

Zhu Jianjiang J Qi Hong H Cao Sha S Cai Lirong L Wen Xiaohui X Tang Guodong G Wan Qian Q Chen Chen C Wang Juan J Zeng Wen W Luo Yao Y

Molecular genetics & genomic medicine 20190717 9

<h4>Background</h4>The 18p terminal deletion with inverted duplication is an extremely rare chromosome structure abnormality and the common clinical manifestations include intellectual disability and speech delay, etc. Up to now, only three confirmed cases were reported in Europe, and here, for the first time in the Asian population, we report a case of de novo 18p inv-dup-del in a Chinese pregnant woman. This structural variation was accidentally discovered by the noninvasive prenatal testing ( ...[more]

PMID: 31317671

Similar Datasets

Project description:BACKGROUND:Intellectual disability (ID) is a complex condition that can impact multiple domains of development. The genetic contribution to ID's etiology is significant, with more than 100 implicated genes and loci currently identified. The majority of such variants are rare and de novo genetic mutations. METHODS:We have applied whole-genome microarray to identify large, rare, clinically relevant copy number variants (CNVs). We have applied well-established algorithms for variants call. Quantitative polymerase chain reaction (qPCR) was applied to validate the variants using three technical replicates for each family member. To assess whether the copy number variation was due to balanced translocation or mosaicism, we further conducted droplet digital PCR (ddPCR) on the whole family. We have, as well, applied "critical-exon" mapping, human developmental brain transcriptome, and a database of known associated neurodevelopmental disorder variants to identify candidate genes. RESULTS:Here we present two siblings who are both impacted by a large terminal duplication and a deletion. Whole-genome microarray revealed an 18.82 megabase (MB) duplication at terminal locus (7q34-q36.3) of chromosome 7 and a 3.90 MB deletion impacting the terminal locus (15q26.3) of chromosome 15. qPCR and ddPCR experiments confirmed the de novo origin of the variants and the co-occurrence of these two de novo events among the siblings, but their absence in both parents, implicates an unbalanced translocation that could have mal-segregated among the siblings or a possible germline mosaicism. These terminal events impact IGF1R, CNTNAP2, and DPP6, shown to be strongly associated with neurodevelopmental disorders. Detailed clinical examination of the siblings revealed the presence of both shared and distinct phenotypic features. CONCLUSIONS:This study identified two large rare terminal de novo events impacting two siblings. Further phenotypic investigation highlights that even in the presence of identical large high penetrant variants, spectrum of clinical features can be different between the siblings.

Dataset Information

Detection of a rare de novo 18p terminal deletion with inverted duplication in a Chinese pregnant woman.

Background

Methods

Results

Conclusion

Publications

Detection of a rare de novo 18p terminal deletion with inverted duplication in a Chinese pregnant woman.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure