BACKGROUND: Conventional PCR-based direct sequencing of candidate genes for a 
family with X-linked leucoencephalopathy with unknown aetiology failed to 
identify any causative mutations.
OBJECTIVE: To carry out exome sequencing of entire transcripts of the whole X 
chromosome to investigate a family with X linked leucoencephalopathy.
METHODS AND RESULTS: Next-generation sequencing of all the transcripts of the X 
chromosome, after liquid-based genome partitioning, was performed on one of the 
two affected male subjects (the proband) and an unaffected male subject (his 
brother). A nonsense mutation in MCT8 (c.1102A→T (p.R368X)) was identified in 
the proband. Subsequent PCR-based direct sequencing of other family members 
confirmed the presence of this mutation, hemizygous in the other affected 
brother and heterozygous in the proband's mother and maternal grandmother. MCT8 
mutations usually cause abnormal thyroid function in addition to neurological 
abnormalities, but this proband had normal thyroid function.
CONCLUSION: Single-lane exome next-generation sequencing is sufficient to fully 
analyse all the transcripts of the X chromosome. This method is particularly 
suitable for mutation screening of X-linked recessive disorders and can avoid 
biases in candidate gene choice.