ATP7A-Related Copper Transport Disorders (ATP7A) Sequencing and Deletion/Duplication

Background Information for ATP7A-Related Copper Transport Disorders (ATP7A) Sequencing and Deletion/Duplication
Characteristics: Menkes disease, occipital horn syndrome, and ATP7A-related distal motor neuropathy are disorders of copper transport due to mutations in the ATP7A gene. Individuals with Menkes disease may present in the infant period with loss of milestones, abnormal hair, lethargy, hypotonia, and seizures.  Occipital horn syndrome shares many features with Menkes disease but has a less severe neurological phenotype.
Inheritance: X-linked.
Cause: Pathogenic ATP7A gene mutations.
Clinical Sensitivity: 95 percent for Menkes disease and occipital horn syndrome; unknown for ATP7A-related distal motor neuropathy.
Methodology: Bidirectional sequencing of all coding regions and intron-exon boundaries of the ATP7A gene; Multiplex Ligation-dependent Probe Amplification (MLPA) to detect large ATP7A deletions/duplications.
Analytical Sensitivity and Specificity: 99 percent for sequencing; 99 percent and 95 percent for MLPA respectively.
Limitations: Diagnostic errors can occur due to rare sequence variations. Regulatory region mutations and deep intronic mutations will not be detected. The breakpoints of large deletions/duplications will not be determined. Mutations in genes other than ATP7A will not be detected.