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DOI: 10.1055/s-0040-1715639
A Novel SETBP1 Gene Disruption by a De Novo Balanced Translocation in a Patient with Speech Impairment, Intellectual, and Behavioral Disorder
Funding This work was supported by AMED under the grant numbers JP19ek0109280, JP19dm0107090, JP19ek0109301, JP19ek0109348, and JP18kk020501 (to N. Matsumoto); JSPS KAKENHI under the grant numbers JP17H01539 (to N. Matsumoto) and JP19H03621 (to N. Miyake); grants from the Ministry of Health, Labor, and Welfare (to N. Matsumoto); and the Takeda Science Foundation (to N. Matsumoto and N. Miyake).Abstract
Balanced chromosomal abnormalities (BCAs) can disrupt gene function resulting in disease. To date, BCA disrupting the SET binding protein 1 (SETBP1) gene has not been reported. On the other hand, de novo heterozygous variants in the highly conserved 11-bp region in SETBP1 can result in the Schinzel–Giedion syndrome. This condition is characterized by severe intellectual disability, a characteristic face, and multiple-system anomalies. Further other types of mutations involving SETBP1 are associated with a different phenotype, mental retardation, autosomal dominant 29 (MRD29), which has mild dysmorphic features, developmental delay, and behavioral disorders. Here we report a male patient who has moderate intellectual disability, mild behavioral difficulties, and severe expressive speech impairment resulting from a de novo balanced chromosome translocation, t(12;18)(q22;q12.3). By whole genome sequencing, we determined the breakpoints at the nucleotide level. The 18q12.3 breakpoint was located between exons 2 and 3 of SETBP1. Phenotypic features of our patient are compatible with those with MRD29. This is the first reported BCA disrupting SETBP1.
* I.V.B. and F.S. contributed equally to this study.
Publication History
Received: 15 June 2020
Accepted: 10 July 2020
Article published online:
31 August 2020
© 2020. Thieme. All rights reserved.
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