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Clinical Report: Warsaw Breakage Syndrome with small radii and fibulae
Author(s) -
Eppley Sarah,
Hopkin Robert J.,
Mendelsohn Bryce,
Slavotinek Anne M.
Publication year - 2017
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.38382
Subject(s) - microcephaly , nijmegen breakage syndrome , bloom syndrome , sanger sequencing , hearing loss , fanconi anemia , genetics , biology , short stature , exome sequencing , frameshift mutation , sensorineural hearing loss , pediatrics , medicine , mutation , gene , ataxia telangiectasia , audiology , dna repair , dna , helicase , rna , dna damage
We present two new cases of Warsaw Breakage Syndrome (WABS), an autosomal recessive cohesinopathy, in sisters aged 13 and 11 years who both had compound heterozygous mutations in DDX11 . After exclusion of Fanconi anemia, Bloom syndrome and Nijmegen breakage syndrome, whole exome sequencing revealed two novel variants—c.1523T>G, predicting (p.Leu508Arg) and c.1949‐1G>A (IVS19‐1G>A), that were confirmed with Sanger sequencing in both affected individuals. DDX11 encodes an iron‐sulfur‐containing DNA helicase, and mutations in this gene have been reported in the five WABS cases previously identified to date. The sisters reported here display the distinguishing clinical features of WABS: pre‐ and post‐natal growth restriction, microcephaly, intellectual disability, sensorineural hearing loss with cochlear abnormalities, and facial dysmorphic features. In addition, our cases had early menarche at 8 and 10 years of age, bilateral small thumbs, and the younger, more severely affected sister had small fibulae. These findings broaden the WABS phenotype and the limb malformations demonstrate further clinical overlap with Fanconi anemia and other cohesinopathies, such as Roberts Syndrome.