Multigeneration Inheritance through Fertile XX Carriers of an NR0B1 (DAX1) Locus Duplication in a Kindred of Females with Isolated XY Gonadal Dysgenesis

• A 160 kb minimal common region in Xp21 has been determined as the cause of XY gonadal dysgenesis, if duplicated. The region contains theMAGEBgenes and theNR0B1gene; this is the candidate for gonadal dysgenesis if overexpressed. Most patients present gonadal dysgenesis within a more complex phenotype. However, few independent cases have recently been described presenting with isolated XY gonadal dysgenesis caused by relatively smallNR0B1locus duplications. We have identified anotherNR0B1duplication in two sisters with isolated XY gonadal dysgenesis with an X-linked inheritance pattern. We performed X-inactivation studies in three fertile female carriers of three different smallNR0B1locus duplications identified by our group. The carrier mothers did not show obvious skewing of X-chromosome inactivation, suggesting thatNR0B1overexpression does not impair ovarian function. We furthermore emphasize the importance to investigate theNR0B1locus also in patients with isolated XY gonadal dysgenesis.

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)