Barth syndrome is an X-linked cardiomyopathy with neutropenia and 
3-methylglutaconic aciduria. Recently, mutations in the G4.5 gene, located in 
Xq28, have been described in four probands with Barth syndrome. We have now 
evaluated 14 Barth syndrome pedigrees for mutations in G4.5 and have identified 
unique mutations in all, including four splice-site mutations, three deletions, 
one insertion, five missense mutations, and one nonsense mutation. Nine of the 
14 mutations are predicted to significantly disrupt the protein products of 
G4.5. The occurrence of missense mutations in exons 3 and 8 suggests that these 
exons encode essential portions of the G4. 5 proteins, whose functions remain 
unknown. We found no correlation between the location or type of mutation and 
any of the clinical or laboratory abnormalities of Barth syndrome, which 
suggests that additional factors modify the expression of the Barth phenotype. 
The characterization of mutations of the G4.5 gene will be useful for carrier 
detection, genetic counseling, and the identification of patients with Barth 
syndrome who do not manifest all of the cardinal features of this disorder.