Abstract
Duplications involving the X chromosome, in which the duplicated region is not subject to inactivation, are rare. We describe four distal Xq duplications, in three males and one female, in which the duplicated X chromosomal material is active in all cells. The infantile phenotype bears some resemblance to that of the Prader–Willi syndrome, presenting with initial feeding difficulties, hypotonia and, sometimes, with cryptorchidism. However, the severity of the phenotype is not simply related to the size of the duplication and so variations in gene expression, gene disruption or position effects from breakpoints should be considered as explanations. We have compared the clinical, cytogenetic and molecular findings of our patients with those previously reported. This has enabled us to question the suggestion that duplication of the gene SOX3 is the cause of hypopituitarism and that duplication of Filamin A is the cause of bilateral periventricular nodular heterotopia/mental retardation syndrome (BPNH/MR). We have also narrowed the putative critical interval for X-linked spina bifida.
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Acknowledgements
We are very grateful to the families for participating in this research and also to Sam Baker, Chrisy Joyce and Nikki Savage for cytogenetic diagnosis, to Nicholas R Dennis for encouragement and for reading the manuscripts and the Wellcome Trust who supported the research.
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Lachlan, K.L., Collinson, M.N., Sandford, R.O.C. et al. Functional disomy resulting from duplications of distal Xq in four unrelated patients. Hum Genet 115, 399–408 (2004). https://doi.org/10.1007/s00439-004-1175-x
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DOI: https://doi.org/10.1007/s00439-004-1175-x