Further Clinical and Molecular Delineation of Xp11.22 Deletion Syndrome: A Case Report

Abstract

Intellectual disability (ID) is the most common diagnosis noted among children with genetic disorders. It causes social and economic burden to families and communities. The genetic causes are not completely understood, and there is significant heterogeneity. Recently, a new chromosomal X-linked syndrome was reported to cause ID. Four males were described from three families with ID, developmental delay, hypotonia, joint hypermobility, and relative macrocephaly. They all carried small, overlapping Xp11.22 deletions. To date, the described smallest region of overlapping deletion at this locus spanned ~ 430 kb) and included four genes (CENPVL1, CENPVL2, MAGED1, and GSPT2), which are proposed as the main drivers of the phenotype. We describe a male patient who matches the phenotype and contributes to defining a narrow phenocritical region at Xp11.22. We propose that GSPT2 loss-of-function might be the probable cause of the phenotypic features seen in these patients.

Keywords: Chromosome Xp11.3 Deletion Syndrome; GSPT2 protein, human; Intellectual Disability; MAGED1 protein, human; Microarray Analysis.

Figure 1

Schematic representation of the Xp11.22 deletions. The deletions of each subject are shown in relation to the position of Xp11.22 genes. The coordinates shown at the top of the figure are based on hg19. The RefSeq genes located in this critical region—CENPVL1, CENPVL2, GSPT2, and MAGED1—are shown in red. Genes depicted in blue are deleted in a subset of subjects 1–4, but not in our patient. Genes depicted in gray were not deleted in any subject.