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

Abstract
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.