Skip to Main content Skip to Navigation
Journal articles

De novo complex X chromosome rearrangement unmasking maternally inherited CSF2RA deletion in a girl with pulmonary alveolar proteinosis

Abstract : 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 (CSF2RA) gene deletion. Consistent with the recessive mode of inheritance, the de novo paternal Xp22.33p22.2 deletion combined to the maternally inherited CSF2RA gene deletion led to homozygous deletion of CSF2RA 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 (SHOX) 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.
Document type :
Journal articles
Complete list of metadata

https://hal.univ-lorraine.fr/hal-01701044
Contributor : Ngere Ul <>
Submitted on : Monday, February 5, 2018 - 3:23:43 PM
Last modification on : Tuesday, October 13, 2020 - 10:47:39 AM

Links full text

Identifiers

Citation

Julie Auger, Céline Bonnet, Mylène Valduga, Christophe Philippe, Emmanuelle Bertolo-Houriez, et al.. De novo complex X chromosome rearrangement unmasking maternally inherited CSF2RA deletion in a girl with pulmonary alveolar proteinosis. American Journal of Medical Genetics Part A, Wiley, 2013, pp.n/a - n/a. ⟨10.1002/ajmg.a.36097⟩. ⟨hal-01701044⟩

Share

Metrics

Record views

141