ATRX syndrome in a girl with a heterozygous mutation in the <i>ATRX</i> 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.