De novo complex X chromosome rearrangement unmasking maternally inherited CSF2RA deletion in a girl with pulmonary alveolar proteinosis. Issue 10 (5th August 2013)

• Record Type: Journal Article
• Authors: Auger, Julie; Bonnet, Céline; Valduga, Mylène; Philippe, Christophe; Bertolo‐Houriez, Emmanuelle; Beri‐Dexheimer, Mylène; Schweitzer, Cyril; Leheup, Bruno; Jonveaux, Philippe
• Is Part Of: American journal of medical genetics. Volume 161:Issue 10(2013:Oct.)
• Page Start: 2594
• Page End: 2599
• Publication Date: 2013-08-05
• Subjects: Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.36097
• Languages: English
• ISSNs: 1552-4825

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="ajmga36097-sec-0001" sec-type="section"> <p>We report on a 3‐year‐old girl with a de novo complex X chromosome rearrangement associated with congenital pulmonary alveolar proteinosis (PAP) and short stature. Array comparative genome hybridization and FISH analyses contributed to characterize the complex rearrangement consisting of a 7.37 Mb terminal deletion of Xp22.33p22.2, a 17.3 Mb interstitial inverted duplication of Xp22.2p21.3, and a 10.14 Mb duplication of Xq27.3q28. PCR analysis of microsatellite markers supported a paternal origin of the X chromosome rearrangement. A pre‐meiotic two‐step mechanism may explain the occurrence of this complex X rearrangement: an inverted duplication deletion event on Xp, and duplication of the Xq27.3qter region through a telomere capture event stabilizing the broken chromosome Xp end. The girl has also inherited from her healthy mother an X chromosome with a colony stimulating factor 2 receptor, alpha (<italic>CSF2RA</italic>) gene deletion. Consistent with the recessive mode of inheritance, the de novo paternal Xp22.33p22.2 deletion combined to the maternally inherited <italic>CSF2RA</italic> gene deletion led to homozygous deletion of <italic>CSF2RA</italic> and PAP diagnosis in the girl. The Xp deletion encompasses the pseudoautosomal region 1 (PAR1) which contains genes that escape X inactivation. Short stature homeobox (<italic>SHOX</italic>) haploinsufficiency explains growth retardation. Absence of other symptoms in relation to the X deletion/amplification is most probably due to skewed X inactivation. Finally, inherited deletions may unmask rare pathogenic genomic rearrangement and contribute to clinical phenotypes by a recessive mode of gene action. © 2013 Wiley Periodicals, Inc.</p> </sec> </abstract>