Absence of learning difficulties in a hyperactive boy with a terminal Xp deletion encompassing the MRX49 locus

X-linked ichthyosis (steroid sulfatase deficiency) is associated with increased risk of attention deficit hyperactivity disorder, autism and social communication deficits

“…Other reports have demonstrated a highly variable phenotype associated with VCX3A deletions including normal intellectual development 2 3 8 10 27. A recent study of 80 XLI cases with normal IQ identified 62 with the common deletion and detailed breakpoint analysis showed they all had loss of VCX3A 28.…”

“…It is possible that loss of these genes may be contributing to the more severe phenotype but it is clear from the literature that there is no simple genotype–phenotype correlation. Some published cases with deletion of this region have been severely impaired9 29 while others have been more mildly affected and in some cases had normal intellectual development 2 – 4…”

“…Several case reports of patients with Xp deletions and XLI include cognitive behavioural features such as attention deficit hyperactivity disorder (ADHD),2 – 4 mental retardation4 – 10 and autism 7 9. The VCX3A gene (variably charged, X chromosome, 3A; also known as VCX-A ) has been proposed to have a role in the occurrence of mental retardation in some XLI individuals 5 6.…”

Telomeres: a diagnosis at the end of the chromosomes

“…138 139 One gene for short stature, the short stature homeobox containing gene (SHOX), 140 was also shown to be mutated or deleted in families with Leri-Weill dyschondrosteosis. 141 142 Although a putative locus for mental retardation (MRX49) has been located distal to the STS locus, 143 Tobias et al 144 reported a boy with a normal intelligence and a telomeric deletion including the STS locus as the result of a der(X)t(X;Y)(p22.31;q11.21). Clinically there is a much similarity with the case reported by De Vries et al 145 with a submicroscopic Xp22.31-pter deletion with a breakpoint just upstream of the STS locus.…”

Molecular cytogenetic analysis of a familial interstitial deletion Xp22.2‐22.3 with a highly variable phenotype in female carriers

“…This translocation was associated with a deletion of 8-Mb on the X chromosome and the loss of all four VCX genes and a duplication of both VCY genes. In contrast, two other patients with t(X;Y) and ichthyosis were reported with normal intelligence although the VCX-A gene was deleted, while the VCX-B and VCX-C were retained [Tobias et al, 2001;Doherty et al, 2003]. Van Esch et al [2005] concluded that a dosage effect might exist for the VCX/Y group of genes.…”