19q13.11 Microdeletion Concomitant with Ins(2;19)(p25.3;q13.1q13.4)dn in a Boy: Potential Role of UBA2 in the Associated Phenotype

Overview

Journal Mol Cytogenet

Publisher Biomed Central

Specialty Biochemistry

Date 2014 Dec 18

PMID 25516771

Citations 10

Authors

Carlos Venegas-Vega

Karem Nieto-Martinez

Alejandro Martinez-Herrera

Laura Gomez-Laguna

Jaime Berumen

Alicia Cervantes

Susana Kofman

Fernando Fernandez-Ramirez

Affiliations

Soon will be listed here.

Abstract

The 19q13.11 microdeletion syndrome (MIM613026) is a clinically recognisable condition in which a 324-kb minimal overlapping critical region has been recently described. However, genes not included within this region, such as WTIP and UBA2, have been proposed to contribute to the clinical characteristics observed in patients. Using cytogenetic techniques, single nucleotide polymorphism arrays, and the quantitative polymerase chain reaction, we identified a novel case with a 2.49-Mb deletion derived from a de novo chromosomal rearrangement. Based on a review of the literature, we support the notion that UBA2 haploinsufficiency could contribute to the phenotype of this rare genomic disorder. UBA2 belongs to a protein complex with sumoylation activity, and several transcription factors, hormone receptors, and signalling proteins related to brain and sexual development are regulated by this post-translational modification. Additional clinical reports and further research on UBA2 molecular function are warranted.

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References

Shaikh T, Gai X, Perin J, Glessner J, Xie H, Murphy K . High-resolution mapping and analysis of copy number variations in the human genome: a data resource for clinical and research applications. Genome Res. 2009; 19(9):1682-90. PMC: 2752118. DOI: 10.1101/gr.083501.108. View

Komatsu T, Mizusaki H, Mukai T, Ogawa H, Baba D, Shirakawa M . Small ubiquitin-like modifier 1 (SUMO-1) modification of the synergy control motif of Ad4 binding protein/steroidogenic factor 1 (Ad4BP/SF-1) regulates synergistic transcription between Ad4BP/SF-1 and Sox9. Mol Endocrinol. 2004; 18(10):2451-62. DOI: 10.1210/me.2004-0173. View

Chowdhury S, Bandholz A, Parkash S, Dyack S, Rideout A, Leppig K . Phenotypic and molecular characterization of 19q12q13.1 deletions: a report of five patients. Am J Med Genet A. 2013; 164A(1):62-9. DOI: 10.1002/ajmg.a.36201. View

Bragin E, Chatzimichali E, Wright C, Hurles M, Firth H, Bevan A . DECIPHER: database for the interpretation of phenotype-linked plausibly pathogenic sequence and copy-number variation. Nucleic Acids Res. 2013; 42(Database issue):D993-D1000. PMC: 3965078. DOI: 10.1093/nar/gkt937. View

Gana S, Veggiotti P, Sciacca G, Fedeli C, Bersano A, Micieli G . 19q13.11 cryptic deletion: description of two new cases and indication for a role of WTIP haploinsufficiency in hypospadias. Eur J Hum Genet. 2012; 20(8):852-6. PMC: 3400733. DOI: 10.1038/ejhg.2012.19. View

Jackson B, Thompson D, Wright M, McAndrews M, Bernard A, Nebert D . Update of the human secretoglobin (SCGB) gene superfamily and an example of 'evolutionary bloom' of androgen-binding protein genes within the mouse Scgb gene superfamily. Hum Genomics. 2011; 5(6):691-702. PMC: 3251818. DOI: 10.1186/1479-7364-5-6-691. View

Malan V, Raoul O, Firth H, Royer G, Turleau C, Bernheim A . 19q13.11 deletion syndrome: a novel clinically recognisable genetic condition identified by array comparative genomic hybridisation. J Med Genet. 2009; 46(9):635-40. DOI: 10.1136/jmg.2008.062034. View

Huang N, Lee I, Marcotte E, Hurles M . Characterising and predicting haploinsufficiency in the human genome. PLoS Genet. 2010; 6(10):e1001154. PMC: 2954820. DOI: 10.1371/journal.pgen.1001154. View

Nowick K, Hamilton A, Zhang H, Stubbs L . Rapid sequence and expression divergence suggest selection for novel function in primate-specific KRAB-ZNF genes. Mol Biol Evol. 2010; 27(11):2606-17. PMC: 2981486. DOI: 10.1093/molbev/msq157. View

10.

Kulharya A, Michaelis R, Norris K, Taylor H, Garcia-Heras J . Constitutional del(19)(q12q13.1) in a three-year-old girl with severe phenotypic abnormalities affecting multiple organ systems. Am J Med Genet. 1998; 77(5):391-4. View

11.

Gwizdek C, Casse F, Martin S . Protein sumoylation in brain development, neuronal morphology and spinogenesis. Neuromolecular Med. 2013; 15(4):677-91. DOI: 10.1007/s12017-013-8252-z. View

12.

Ulrich H . The SUMO system: an overview. Methods Mol Biol. 2008; 497:3-16. DOI: 10.1007/978-1-59745-566-4_1. View

13.

Franceschini A, Szklarczyk D, Frankild S, Kuhn M, Simonovic M, Roth A . STRING v9.1: protein-protein interaction networks, with increased coverage and integration. Nucleic Acids Res. 2012; 41(Database issue):D808-15. PMC: 3531103. DOI: 10.1093/nar/gks1094. View

14.

Forzano F, Napoli F, Uliana V, Malacarne M, Viaggi C, Bloise R . 19q13 microdeletion syndrome: Further refining the critical region. Eur J Med Genet. 2012; 55(6-7):429-32. DOI: 10.1016/j.ejmg.2012.03.002. View

15.

Schuurs-Hoeijmakers J, Vermeer S, van Bon B, Pfundt R, Marcelis C, de Brouwer A . Refining the critical region of the novel 19q13.11 microdeletion syndrome to 750 Kb. J Med Genet. 2009; 46(6):421-3. DOI: 10.1136/jmg.2009.066910. View

16.

Mukherjee S, Cruz-Rodriguez O, Bolton E, Iniguez-Lluhi J . The in vivo role of androgen receptor SUMOylation as revealed by androgen insensitivity syndrome and prostate cancer mutations targeting the proline/glycine residues of synergy control motifs. J Biol Chem. 2012; 287(37):31195-206. PMC: 3438951. DOI: 10.1074/jbc.M112.395210. View

17.

MacDonald J, Ziman R, Yuen R, Feuk L, Scherer S . The Database of Genomic Variants: a curated collection of structural variation in the human genome. Nucleic Acids Res. 2013; 42(Database issue):D986-92. PMC: 3965079. DOI: 10.1093/nar/gkt958. View