Craniofrontonasal syndrome in a male due to chromosomal mosaicism involving EFNB1: further insights into a genetic paradox. (28th May 2013)

• Record Type: Journal Article
• Authors: Evers, C.; Jungwirth, M.S.; Morgenthaler, J.; Hinderhofer, K.; Maas, B.; Janssen, J.W.G.; Jauch, A.; Hehr, U.; Steinbeisser, H.; Moog, U.
• Is Part Of: Clinical genetics. Volume 85:Number 4(2014:Apr.)
• Page Start: 347
• Page End: 353
• Publication Date: 2013-05-28
• Subjects: Medical genetics -- Periodicals; 616.0420
• DOI: 10.1111/cge.12171
• Languages: English
• ISSNs: 0009-9163

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Craniofrontonasal syndrome (CFNS) is an X‐linked disorder caused by inactivating mutations in the gene for ephrin‐B1 (<italic>EFNB1</italic>). Paradoxically it shows a more severe phenotype in females than in males. As a result of X inactivation cell populations with and without <italic>EFNB1</italic> expression are found in <italic>EFNB1+/−</italic> females. This is thought to initiate a process termed cellular interference which may be responsible for the phenotype in females. We present a boy with severe clinical features of CFNS. In ∼42% of his blood cells we found a supernumerary ring X chromosome containing <italic>EFNB1</italic> but lacking <italic>XIST</italic>. Mosaicism for cell populations with different levels of EFNB1 expression can explain the severe phenotype of this patient. <italic>In vitro</italic> experiments in <italic>Xenopus</italic> tissue showed that cells overexpress ephrinB1 cluster and sort out from wild‐type cells. Our report provides further evidence that cellular interference contributes to the paradoxical inheritance pattern of CFNS.</p> </abstract>