Lyonization effects of the t(X;16) translocation on the phenotypic expression in a rare female with Menkes disease.
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.
Sirleto
Pietro
P
Cytogenetics and Molecular Genetics, Bambino Gesù Children's Hospital, Roma 00165, Italy.
Surace
Cecilia
C
Santos
Helena
H
Bertini
Enrico
E
Tomaiuolo
Anna C
AC
Lombardo
Antonietta
A
Boenzi
Sara
S
Bevivino
Elsa
E
Dionisi-Vici
Carlo
C
Angioni
Adriano
A
D000251:Adenosine Triphosphatases / Q000235:genetics*; D027682:Cation Transport Proteins / Q000235:genetics*; D002536:Cerebral Arteries / Q000473:pathology; D002648:Child; D022202:Chromosomes, Artificial, Bacterial; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D041321:Chromosomes, Human, X / Q000235:genetics*; D000073840:Copper-Transporting ATPases; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D007706:Menkes Kinky Hair Syndrome / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D014178:Translocation, Genetic / Q000235:genetics*; D049951:X Chromosome Inactivation / Q000235:genetics*
D027682:Cation Transport Proteins; D000251:Adenosine Triphosphatases; C081184:ATP7A protein, human; D000073840:Copper-Transporting ATPases