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Am J Med Genet A. 2014 Jul;164A(7):1795-801. doi: 10.1002/ajmg.a.36524. Epub 2014 Apr 3.

Xq28 duplication overlapping the int22h-1/int22h-2 region and including RAB39B and CLIC2 in a family with intellectual and developmental disability.

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  • 1Cytogenetics and Genomic Microarray, ARUP Laboratories, Salt Lake City, Utah; Department of Pathology, University of Utah, Salt Lake City, Utah.

Abstract

Duplications involving terminal Xq28 are a known cause of intellectual disability (ID) in males and in females with unfavorable X-inactivation patterns. Within Xq28, functional disomy of MECP2 causes a severe ID syndrome, however the dosage sensitivity of other Xq28 duplicated genes is less certain. Duplications involving the int22h-1/int22h-2 LCR-flanked region in distal Xq28 have recently been linked to a novel ID-associated phenotype. While evidence for the dosage sensitivity of this region is emerging, the phenotypic contribution of individual genes within the int22h-1/int22h-2-flanked region has yet to be determined. We report a familial case of a novel 774 kb Xq28-qter duplication, detected by cytogenomic microarray analysis, that partially overlaps the int22h-1/int22h-2-flanked region. This duplication and a 570 kb Xpter-p22.33 loss within the pseudoautosomal region were identified in three siblings, one female and two males, who presented with developmental delays/intellectual disability, mild dysmorphic features and short stature. Although unconfirmed, these results are suggestive of maternal inheritance of a recombinant X. We compare our clinical findings to patients with int22h-1/int22h-2-mediated duplications and discuss the potential pathogenicity of genes within the duplicated region, including those within the shared region of overlap, RAB39B and CLIC2.

KEYWORDS:

CLIC2; RAB39B; Xp22.33 deletion; Xq28 duplication; int22h

PMID:
24700761
DOI:
10.1002/ajmg.a.36524
[PubMed - indexed for MEDLINE]
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