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Xq28 duplication overlapping the int22h‐1/int22h‐2 region and including RAB39B and CLIC2 in a family with intellectual and developmental disability
Author(s) -
Andersen Erica F.,
Baldwin Erin E.,
Ellingwood Sara,
Smith Rosemarie,
Lamb Allen N.
Publication year - 2014
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.36524
Subject(s) - xq28 , pseudoautosomal region , gene duplication , genetics , x chromosome , biology , intellectual disability , short stature , gene , endocrinology
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 . © 2014 Wiley Periodicals, Inc.