Xq;autosome translocation in POF: Xq27.2 deletion resulting in haploinsufficiency for SPANX

Abstract

Premature ovarian failure (POF), also called primary ovarian insufficiency (POI), is defined as irregular menses in women younger than 40 years with menopausal-level serum gonadotropins [1]. Spontaneous onset POF may result from numeric and structural chromosomal abnormalities, fragile X premutations, autoimmune disorders and rare syndromes, though in most cases the etiology remains unknown [2]. Structural chromosomal abnormalities, such as deletions and translocations of specific regions on the X chromosome, have been associated with POF. This association may be due to the haploinsufficiency of genes necessary for normal ovarian function. Standard karyotypes and deletion mapping have identified three regions of interest for POI, one in Xp and two in X (POF1: X26-28 and POF2: X13.3-22) [3, 4]. Several candidate genes in X have been proposed by mapping genes interrupted by the breakpoints in X;autosome translocations. These candidate genes include DIAPH2, XPNEP2, DACH2, POF1B, CHM and NXF5, though none of these genes have a well-defined role in POF [5]. Introduction of high-resolution microarray CGH has refined the ability to detect cryptic chromosomal deletions and duplications in the X POF regions, potentially facilitating identification of candidate genes [6]. We present a patient with infertility and primary ovarian insufficiency having a balanced Xq;autosome translocation near the POF2 region, with a cryptic deletion at Xq27.2, identified with array CGH and confirmed by fluorescent in situ hybridization (FISH). The deletion corresponds to the loci for SPANX (sperm protein associated with the nucleus, X-linked), which play roles in spermatogenesis and may represent candidate genes for POF.