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Maple syrup urine disease due to a paracentric inversion of chr 19 that disrupts BCKDHA: A case report

Authors :
Katsuyuki Yokoi
Yoko Nakajima
Yuta Sudo
Tasuku Mariya
Rie Kawamura
Makiko Tsutsumi
Hidehito Inagaki
Tetsushi Yoshikawa
Tetsuya Ito
Hiroki Kurahashi
Source :
JIMD Reports, Vol 63, Iss 6, Pp 575-580 (2022)
Publication Year :
2022
Publisher :
Wiley, 2022.

Abstract

Abstract Maple syrup urine disease (MSUD) is a rare autosomal recessive inherited disorder of branched‐chain amino acid metabolism caused by mutations in BCKDHA, BCKDHB, and DBT that encode the E1α, E1β, and E2 subunits of the branched‐chain α‐ketoacid dehydrogenase (BCKD) complex. Various MSUD‐causing variants have been described; however, no structural rearrangements in BCKDHA have been reported to cause the classic MSUD phenotype. Here, we describe the classic patient with MSUD with compound heterozygous pathogenic variants in BCKDHA: a missense variant (NM_000709.3:c.757G > A, NP_000700.1:p.Ala253Thr) and a paracentric inversion disrupting Intron 1 of BCKDHA, which was identified by whole‐genome sequencing and validated by fluorescence in situ hybridization. Using the sequence information of the breakpoint junction, we gained mechanistic insight into the development of this structural rearrangement. Furthermore, the establishment of junction‐specific polymerase chain reaction could facilitate identification of the variant in case carrier or future prenatal/preimplantation tests are necessary.

Details

Language :
English
ISSN :
21928312
Volume :
63
Issue :
6
Database :
Directory of Open Access Journals
Journal :
JIMD Reports
Publication Type :
Academic Journal
Accession number :
edsdoj.8e7589776bf14c6183443ec6dc96316b
Document Type :
article
Full Text :
https://doi.org/10.1002/jmd2.12333