Background: Warsaw Breakage Syndrome (WABS) is an ultra rare cohesinopathy caused by biallelic mutation of DDX11 gene. It is clinically characterized by pre and postnatal growth delay, microcephaly, hearing loss with cochlear hypoplasia, skin color abnormalities, and dysmorphisms. Methods: Mutational screening and functional analyses (protein expression and 3D-modeling) were performed in order to investigate the presence and pathogenicity of DDX11 variant identified in our patients. Results: We report the clinical history of two sisters affected by WABS with a pathological mytomicin C test carrying compound heterozygous mutations (c.2507T > C / c.907_920del) of the DDX11 gene. The pathogenicity of this variant was confirmed in the light of a bioinformatic study and protein three-dimensional modeling, as well as expression analysis. Conclusion: These findings further extend the clinical and molecular knowledge about the WABS showing a possible mild phenotype without major malformations or intellectual disability.

Two further patients with Warsaw breakage syndrome. Is a mild phenotype possible?

Savoia A.;Gasparini P.;
2019-01-01

Abstract

Background: Warsaw Breakage Syndrome (WABS) is an ultra rare cohesinopathy caused by biallelic mutation of DDX11 gene. It is clinically characterized by pre and postnatal growth delay, microcephaly, hearing loss with cochlear hypoplasia, skin color abnormalities, and dysmorphisms. Methods: Mutational screening and functional analyses (protein expression and 3D-modeling) were performed in order to investigate the presence and pathogenicity of DDX11 variant identified in our patients. Results: We report the clinical history of two sisters affected by WABS with a pathological mytomicin C test carrying compound heterozygous mutations (c.2507T > C / c.907_920del) of the DDX11 gene. The pathogenicity of this variant was confirmed in the light of a bioinformatic study and protein three-dimensional modeling, as well as expression analysis. Conclusion: These findings further extend the clinical and molecular knowledge about the WABS showing a possible mild phenotype without major malformations or intellectual disability.
DDX11
mutations
Warsaw Breakage Syndrome
Abnormalities
Multiple
Cafe-au-Lait Spots
Cell Line
Cells
Cultured
Child
Child
Preschool
DEAD-box RNA Helicases
DNA Helicases
Female
Hearing Loss
Sensorineural
Humans
Mutation
Syndrome
Phenotype
File in questo prodotto:
File Dimensione Formato  
MGG3-7-e639.pdf

non disponibili

Dimensione 621.58 kB
Formato Adobe PDF
621.58 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/1064463
Citazioni
  • ???jsp.display-item.citation.pmc??? 5
  • Scopus 6
  • ???jsp.display-item.citation.isi??? 7
social impact