ATRX syndrome in a girl with a heterozygous mutation in the ATRX Zn finger domain and a totally skewed X‐inactivation pattern

Abstract

Mutations in the X‐encoded gene ATRX are known to give rise to syndromic mental retardation in male patients whereas female carriers show preferential inactivation of the mutated X chromosome and appear healthy. Here, we describe a 4‐year‐old girl with typical features of ATRX syndrome, carrying the recurrent R246C mutation of ATRX. We show that her pattern of X‐inactivation is totally skewed and that her active X chromosome which harbors the ATRX mutation, was maternally inherited. To our knowledge, this is the first report of ATRX syndrome in a female patient. Since she was born after in vitro fertilization (IVF), we propose a possible link between assisted reproduction technologies (ART) and the unexpected X chromosome methylation pattern that we observed.