Xq28 duplication presenting with intestinal and bladder dysfunction and a distinctive facial appearance.
Xq28 duplications encompassing MECP2 have been described in male patients with a severe neurodevelopmental disorder associated with hypotonia and spasticity, severe learning disability and recurrent pneumonia. We identified an Xq28 duplication in three families where several male patients had presented with intestinal pseudo-obstruction or bladder distension. The affected boys had similar dysmorphic facial appearances. Subsequently, we ascertained seven further families where the proband presented with similar features. We demonstrated duplications of the Xq28 region in five of these additional families. In addition to MECP2, these duplications encompassed several other genes already known to be associated with diseases including SLC6A8, L1CAM and Filamin A (FLNA). The two remaining families were shown to have intragenic duplications of FLNA only. We discuss which elements of the Xq28 duplication phenotype may be associated with the various genes in the duplication. We propose that duplication of FLNA may contribute to the bowel and bladder phenotype seen in these seven families.
Medical Genetics Research Group and Regional Genetics Service, St Mary's Hospital, Manchester, UK. Jill.Clayton-Smith@cmmc.nhs.uk
Jill
J
Clayton-Smith
Sarah
S
Walters
Emma
E
Hobson
Emma
E
Burkitt-Wright
Rupert
R
Smith
Annick
A
Toutain
Jeanne
J
Amiel
Stanislas
S
Lyonnet
Sahar
S
Mansour
David
D
Fitzpatrick
Roberto
R
Ciccone
Ivana
I
Ricca
Orsetta
O
Zuffardi
Dian
D
Donnai
D041321:Chromosomes, Human, X / Q000235:genetics*; D019066:Facies; D020440:Gene Duplication; D040181:Genetic Diseases, X-Linked / Q000473:pathology*; D006801:Humans; D007418:Intestinal Pseudo-Obstruction / Q000235:genetics* / Q000473:pathology; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics; D001745:Urinary Bladder Diseases / Q000235:genetics* / Q000473:pathology
C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2