Lyonization Effects of the t(X;16) Translocation on the Phenotypic Expression in a Rare Female With Menkes Disease

作者：Sirleto Pietro; Surace Cecilia^*; Santos Helena; Bertini Enrico; Tomaiuolo Anna C; Lombardo Antonietta; Boenzi Sara; Bevivino Elsa; Dionisi Vici Carlo; Angioni Adriano

来源：Pediatric Research, 2009, 65(3): 347-351.

DOI：10.1203/pdr.0b013e3181973b4e

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 Xq 13.3 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 FMRI (fragile X mental retardation 1) gene polymorphism, hits 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. (Pediatr Res 65: 347-351, 2009)

• 出版日期2009-3