1.5 Mutational spectrum MD is inherited as an X-linked recessive trait and, as expected, the vast majority of patients are males. To date, B210 different mutations (from chromosome aberrations to large deletions or duplications, and single-amino-acid substitutions) affecting ATP7A have been reported.1–9 Chromosome abnormalities affecting ATP7A were detected in eight patients, one male7 and seven female patients. One of the female patients was mosaic for the Turner karyotype and the rest had X;autosome translocations (reviewed in Sirleto et al.8). Approximately one-third of the ATP7A mutations are gross deletions ranging in size from a single exon to deletion of the whole gene except for the first two exons,6,9 and four patients have partial gene duplications.9 The rest comprise B140 different intragenic mutations: missense (34%), nonsense (17%) and splice-site mutations (17%), and deletions/insertions/duplications (32%).1–5,9 There is no obvious correlation between the mutations and the clinical course of MD. However, in general, patients with a milder phenotype (such as OHS) have a higher proportion of mutations, which lead to a partially functional protein or result in reduced amounts of an otherwise normal protein.10 Recently, missense ATP7A mutations have been reported in two families with late-onset X-linked hereditary distal motor neuropathy without signs of copper deficiency.11