Diagnosis of Shashi-Pena Syndrome Caused by Chromosomal Rearrangement Using Nanopore Sequencing. (December 2021)

• Record Type: Journal Article
• Authors: Wang, Ya; Tan, Jianxin; Wang, Yan; Liu, An; Qiao, Fengchang; Huang, Mingtao; Zhang, Cuiping; Zhou, Jing; Hu, Ping; Xu, Zhengfeng
• Is Part Of: Neurology. Volume 7:Number 6(2021)
• Publication Date: 2021-12
• Subjects: Neurogenetics -- Periodicals; 616.80442
• DOI: 10.1212/NXG.0000000000000635
• Languages: English
• ISSNs: 2376-7839

Abstract

Abstract : Background and Objectives: The aim of this study was to uncover the genetic cause of delayed psychomotor development and variable intellectual disability in a proband whose previous genetic analyses, including chromosome microarray and whole exome sequencing, had been negative. Methods: Long-read sequencing Oxford Nanopore Technology and RNA-seq analysis were performed on peripheral blood mononuclear cells. Genes with a fold change ≥ 1.5 and p ⩽ 0.05 were identified as differentially expressed. Results: Clinical examinations showed that the proband's features were similar to a rare autosomal-dominant neurodevelopmental syndrome, Shashi-Pena syndrome (MIM #617190). Karyotyping showed that a chromosomal balanced translocation t(2; 11) (p23; q23) was detected in the proband, her father, and her grandmother. Meanwhile, long-read sequencing identified 102 balanced translocations and 145 inversions affecting ASXL2 at an average of 15×. Combined with the family's RNA-seq results, the average mRNA expression of ASXL2 decreased in the patients. Discussion: We identified a complex chromosomal rearrangement affecting ASXL2 as a pathogenic mechanism of Shashi-Pena syndrome in a Chinese family. This case study suggests that nanopore sequencing is suitable for pathogenic analysis of complex rearrangements, providing new avenues for the diagnosis of genetic diseases.