A novel splicing mutation of the ATRX gene in ATR-X syndrome

X-linked α-thalassemia/mental retardation syndrome (ATR-X, MIM#301040) is an X-linked recessive condition affecting males. ATR-X is characterized by severe mental retardation, mild HbH disease, dysmorphic facies, and genital and skeletal abnormalities. ATR-X is caused by mutations in the ATRX gene. Most mutations affect two functionally important domains, the ADD domain and the helicase domain. Here, we report on two brothers with the ATR-X phenotype without HbH disease; both had a mutation in the 5′ upstream region of the ADD domain of the ATRX gene. This mutation was a G to T nucleotide substitution at the 3′ end of exon 5 and resulted in splicing out of exons 5 and 6. Analysis of cDNA structure may clarify genotype–phenotype correlations in ATR-X because splicing mutation could be detectable only by cDNA analysis.