J Pediatr Genet 2022; 11(02): 135-138
DOI: 10.1055/s-0040-1715639
Case Report

A Novel SETBP1 Gene Disruption by a De Novo Balanced Translocation in a Patient with Speech Impairment, Intellectual, and Behavioral Disorder

Ivona Vrkić Boban*
1   Department of Pediatrics, University Hospital of Split, Split, Croatia
,
Futoshi Sekiguchi*
2   Department of Human Genetics, Yokohama City University Graduate School of Medicine, Kanazawa-ku, Yokohama, Japan
,
Mirela Lozić
3   School of Medicine, University of Split, Split, Croatia
,
Noriko Miyake
2   Department of Human Genetics, Yokohama City University Graduate School of Medicine, Kanazawa-ku, Yokohama, Japan
,
Naomichi Matsumoto
2   Department of Human Genetics, Yokohama City University Graduate School of Medicine, Kanazawa-ku, Yokohama, Japan
,
Bernarda Lozić
1   Department of Pediatrics, University Hospital of Split, Split, Croatia
3   School of Medicine, University of Split, Split, Croatia
› Author Affiliations
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.


Supplementary Material



Publication History

Received: 15 June 2020

Accepted: 10 July 2020

Article published online:
31 August 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Jacobs PA, Browne C, Gregson N, Joyce C, White H. Estimates of the frequency of chromosome abnormalities detectable in unselected newborns using moderate levels of banding. J Med Genet 1992; 29 (02) 103-108
  • 2 Warburton D. De novo balanced chromosome rearrangements and extra marker chromosomes identified at prenatal diagnosis: clinical significance and distribution of breakpoints. Am J Hum Genet 1991; 49 (05) 995-1013
  • 3 Marshall CR, Noor A, Vincent JB. et al. Structural variation of chromosomes in autism spectrum disorder. Am J Hum Genet 2008; 82 (02) 477-488
  • 4 Redin C, Brand H, Collins RL. et al. The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies. Nat Genet 2017; 49 (01) 36-45
  • 5 Lei M, Mitsuhashi S, Miyake N. et al. Translocation breakpoint disrupting the host SNHG14 gene but not coding genes or snoRNAs in typical Prader-Willi syndrome. J Hum Genet 2019; 64 (07) 647-652
  • 6 Li H, Durbin R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 2009; 25 (14) 1754-1760
  • 7 Chen K, Wallis JW, McLellan MD. et al. BreakDancer: an algorithm for high-resolution mapping of genomic structural variation. Nat Methods 2009; 6 (09) 677-681
  • 8 Suzuki T, Tsurusaki Y, Nakashima M. et al. Precise detection of chromosomal translocation or inversion breakpoints by whole-genome sequencing. J Hum Genet 2014; 59 (12) 649-654
  • 9 Minakuchi M, Kakazu N, Gorrin-Rivas MJ. et al. Identification and characterization of SEB, a novel protein that binds to the acute undifferentiated leukemia-associated protein SET. Eur J Biochem 2001; 268 (05) 1340-1351
  • 10 Hoischen A, van Bon BWM, Gilissen C. et al. De novo mutations of SETBP1 cause Schinzel-Giedion syndrome. Nat Genet 2010; 42 (06) 483-485
  • 11 Buysse K, Menten B, Oostra A, Tavernier S, Mortier GR, Speleman F. Delineation of a critical region on chromosome 18 for the del(18)(q12.2q21.1) syndrome. Am J Med Genet A 2008; 146A (10) 1330-1334
  • 12 Cody JD, Sebold C, Malik A. et al. Recurrent interstitial deletions of proximal 18q: a new syndrome involving expressive speech delay. Am J Med Genet A 2007; 143A (11) 1181-1190
  • 13 Coe BP, Witherspoon K, Rosenfeld JA. et al. Refining analyses of copy number variation identifies specific genes associated with developmental delay. Nat Genet 2014; 46 (10) 1063-1071
  • 14 Filges I, Shimojima K, Okamoto N. et al. Reduced expression by SETBP1 haploinsufficiency causes developmental and expressive language delay indicating a phenotype distinct from Schinzel-Giedion syndrome. J Med Genet 2011; 48 (02) 117-122
  • 15 Marseglia G, Scordo MR, Pescucci C. et al. 372 kb microdeletion in 18q12.3 causing SETBP1 haploinsufficiency associated with mild mental retardation and expressive speech impairment. Eur J Med Genet 2012; 55 (03) 216-221
  • 16 Perdue MV, Mascheretti S, Kornilov SA. et al. Common variation within the SETBP1 gene is associated with reading-related skills and patterns of functional neural activation. Neuropsychologia 2019; 130: 44-51
  • 17 Panagopoulos I, Kerndrup G, Carlsen N, Strömbeck B, Isaksson M, Johansson B. Fusion of NUP98 and the SET binding protein 1 (SETBP1) gene in a paediatric acute T cell lymphoblastic leukaemia with t(11;18)(p15;q12). Br J Haematol 2007; 136 (02) 294-296
  • 18 Thorvaldsdóttir H, Robinson JT, Mesirov JP. Integrative Genomics Viewer (IGV): high-performance genomics data visualization and exploration. Brief Bioinform 2013; 14 (02) 178-192