A Small Supernumerary Xp Marker Chromosome Including Genes <b><i>NR0B1</i></b> and <b><i>MAGEB</i></b> Causing Partial Gonadal Dysgenesis and Gonadoblastoma
Copy number variations of several genes involved in the process of gonadal determination have been identified as a cause of 46,XY differences of sex development. We report a non-syndromic 14-year-old female patient who was referred with primary amenorrhea, absence of breast development, and atypical genitalia. Her karyotype was 47,XY,+mar/46,XY, and FISH analysis revealed the X chromosome origin of the marker chromosome. Array-CGH data identified a pathogenic 2.0-Mb gain of an Xp21.2 segment containing <i>NR0B1/DAX1</i> and a 1.9-Mb variant of unknown significance from the Xp11.21p11.1 region. This is the first report of a chromosomal microarray analysis to reveal the genetic content of a small supernumerary marker chromosome detected in a 47,XY,+der(X)/46,XY karyotype in a non-syndromic girl with partial gonadal dysgenesis and gonadoblastoma. Our findings indicate that the mosaic presence of the small supernumerary Xp marker, encompassing the <i>NR0B1/DAX1</i> gene, may have been the main cause of dysgenetic testes development, although the role of <i>MAGEB</i> and other genes mapped to the Xp21 segment could not be completely ruled out.
