engleski

Microduplication of Xp22.31 region involving the STS gene in two males with intellectual disability

Genomic instability is a feature of the human Xp22.31 region: deletions, duplications, triplications and other complex rearrangements were identified at this locus. Submicroscopic duplication of Xp22.31 has been reported as either a possible cause of neurobehavioral phenotypes or a benign variant. Recently, two large cohorts of patients with the microduplication at Xp22.31 were reported. The size of the Xp22.31 duplication varied between 149 kb and 1.9 Mb and mostly included the steroid sulfatase (STS) gene. Patients with Xp22.31 recurrent duplications generally presented with a neurocognitive and behavioral phenotype, including developmental delay. The STS gene could be a candidate gene contributing to the abnormal phenotype in Xp22.31 duplication. Here we report 2 boys with the microduplication of Xp22.31 found by MLPA analysis. The duplication was minimum 246, 2 kb in size and included STS and HDHD1A genes. Both of them presented with mild to moderate intellectual disability/developmental delay mainly affecting speak ability, behavioural abnormalities and minor facial dysmorphisms. Proband B also had a hypotonia. The mother of proband A, carrying the same duplication, had a mild intellectual disability. Our cases overlap with those previously described in most clinical features. Although there is no clear evidence to support pathogenicity of the Xp22.31 duplication, there is still enough evidence to consider the Xp22.31 duplication as a risk or modifier factor for intellectual disability and behavioural problems. We hope that the description of these two cases will contribute to the phenotype delineation and elucidation of the role of Xp22.31 duplication.

Microduplication; Xp22.31; STS; intellectual disability

nije evidentirano