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ORIGINAL RESEARCH article

Front. Genet.
Sec. Genetics of Common and Rare Diseases
Volume 15 - 2024 | doi: 10.3389/fgene.2024.1452498

Detection of inversion with breakpoint in ARSB causing MPSVI by whole genome sequencing: Lessons Learned and Best Practice

Provisionally accepted
Yufeng Huang Yufeng Huang Wenyue Deng Wenyue Deng Hui Huang Hui Huang Xiankai Zhang Xiankai Zhang Xiaohong Chen Xiaohong Chen Jian Ye Jian Ye Sukun Luo Sukun Luo Ting Yu Ting Yu Hui Yao Hui Yao Hao Du Hao Du Xuelian He Xuelian He *
  • Wuhan Children’s Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hebei Province, China

The final, formatted version of the article will be published soon.

    Mucopolysaccharidosis type VI (MPSVI), an autosomal recessive lysosomal storage disorder caused by pathogenic variants in ARSB gene. Usually, whole exome sequencing (WES) can identify these variants, and if WES failed to detect causative variants, whole-genome sequencing (WGS) may be considered to investigate deep intronic variations and structural alterations in patients. This study describes a case of a boy diagnosed with MPSVI based on clinical phenotypes and laboratory biochemical assays, and WES identified only a maternally inherited missense variant, c.908G>T (p.Gly303Val), in the ARSB gene. By performing WGS, we found a paracentric inversion involving chromosome 5q14.1q13.2 (78180730-138771424 inv), disrupting the ARSB gene on the proband and his father. The inversion was confirmed through karyotyping analysis, and the breakpoints were validated by agarose gel electrophoresis and Sanger sequencing. This study reminds us that WGS should be done when WES failed to achieve a molecular diagonosis, and it also underscores the importance of WGS especially in cases of high clinical suspicion.

    Keywords: Mucopolysaccharidosis type VI, whole genome sequencing, ArsB, inversion, breakpoint

    Received: 21 Jun 2024; Accepted: 02 Dec 2024.

    Copyright: © 2024 Huang, Deng, Huang, Zhang, Chen, Ye, Luo, Yu, Yao, Du and He. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Xuelian He, Wuhan Children’s Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hebei Province, China

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