Abstract
Menkes disease (MD) is a rare and severe X-linked recessive disorder of copper metabolism. The MD gene, ATP7A (ATPase Cu++ transporting alpha polypeptide), encodes an ATP-dependent copper-binding membrane protein. In this report, we describe a girl with typical clinical features of MD, carrying a balanced translocation between the chromosomes X and 16 producing the disruption of one copy of ATP7A gene and the silencing of the other copy because of the chromosome X inactivation. Fluorescence in situ hybridization experiments with bacterial derived artificial chromosome probes revealed that the breakpoints were located within Xq13.3 and 16p11.2. Replication pattern analysis demonstrated that the normal X chromosome was late replicating and consequently inactivated, whereas the der(X)t(X;16), bearing the disrupted ATP7A gene, was active. An innovative approach, based on FMR1 (fragile X mental retardation 1) gene polymorphism, has been used to disclose the paternal origin of the rearrangement providing a new diagnostic tool for determining the parental origin of defects involving the X chromosome and clarifying the mechanism leading to the cytogenetic rearrangement that occurred in our patient.
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Abbreviations
- ATP7A:
-
ATPase Cu++ transporting alpha polypeptide
- BAC:
-
bacterial artificial chromosome
- BrdU:
-
5-Bromo-2′-deoxyuridine
- FMR1:
-
fragile X mental retardation 1
- MD:
-
Menkes disease
- WCP:
-
whole chromosome painting probe
- XIST:
-
X inactive-specific transcript
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Sirleto, P., Surace, C., Santos, H. et al. Lyonization Effects of the t(X;16) Translocation on the Phenotypic Expression in a Rare Female With Menkes Disease. Pediatr Res 65, 347–351 (2009). https://doi.org/10.1203/PDR.0b013e3181973b4e
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DOI: https://doi.org/10.1203/PDR.0b013e3181973b4e
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