Back to Journals » The Application of Clinical Genetics » Volume 12

Spotlight on Warsaw Breakage Syndrome

Authors Pisani FM

Received 25 September 2019

Accepted for publication 13 November 2019

Published 5 December 2019 Volume 2019:12 Pages 239—248

DOI https://doi.org/10.2147/TACG.S186476

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Mr Davin Leif

Peer reviewer comments 3

Editor who approved publication: Prof. Dr. Martin H. Maurer


Francesca M Pisani

Istituto di Biochimica e Biologia Cellulare, Consiglio Nazionale delle Ricerche, Naples 80131, Italy

Correspondence: Francesca M Pisani
Istituto di Biochimica e Biologia Cellulare, Consiglio Nazionale delle Ricerche, Via P. Castellino, 111, Naples, Italy
Tel +39 –  0816132292
Fax +39 0816132277
Email francesca.pisani@ibbc.cnr.it

Abstract: Warsaw breakage syndrome (WABS) is a very rare recessive hereditary disease caused by mutations in the gene coding for the DNA helicase DDX11, involved in genome stability maintenance and sister cohesion establishment. Typical clinical features observed in WABS patients include growth retardation, facial dysmorphia, microcephaly, hearing loss due to cochlear malformations and, at cytological level, sister chromatid cohesion defects. Molecular bases of WABS have not yet been elucidated, due to lack of disease animal model systems and limited knowledge of the DDX11 physiological functions. However, WABS is considered to belong to the group of cohesinopathies, genetic disorders due to mutations of subunits or regulators of cohesin, the protein complex responsible for tethering sister chromatids from the time of their synthesis till they separate in mitosis. Recent evidences suggest that cohesin and its regulators have additional key roles in chromatin organization by promoting the formation of chromatin loops. This “non-canonical” function of cohesin is expected to impact gene transcription during cell differentiation and embryonic development and its dis-regulation, caused by mutation/loss of genes encoding cohesin subunits or regulators, could originate the developmental defects observed in cohesinopathies. Ethiopathogenesis of WABS is discussed in line with these recent findings and evidence of a possible role of DDX11 as a cohesin regulator.

Keywords: cohesinopathies, developmental disorders, Warsaw breakage syndrome, DDX11, genome stability, sister chromatid cohesion

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