Non‐skewed X‐inactivation may cause mental retardation in a female carrier of X‐linked α‐thalassemia/mental retardation syndrome (ATR‐X): X‐inactivation study of nine female carriers of ATR‐X

X‐linked α‐thalassemia/mental retardation syndrome (ATR‐X) is a syndromic form of X‐linked mental retardation. We investigated the X‐inactivation status of nine female ATR‐X carriers by methylation‐specific PCR of the HUMARA gene. Six carriers demonstrated a skewed X‐inactivation pattern (>90:10) and one showed a non‐skewed pattern (72:28), while two were uninformative because of homozygosity for the CAG repeat polymorphic alleles in the HUMARA . Only the carrier mother who showed non‐skewed X‐inactivation had moderate mental retardation. These findings suggest that mutations in ATRX may cause mental retardation in females, if the X chromosome carrying mutated ATRX is not properly inactivated. © 2005 Wiley‐Liss, Inc.