Ovarian dysgenesis associated with an unbalanced X;6 translocation: first characterisation of reproductive anatomy and cytogenetic evaluation in partial trisomy 6 with breakpoints at Xq22 and 6p23

The aim of this study was to describe the clinical and laboratory findings associated with a previously unreported unbalanced X;6 translocation. Physical examination, reproductive history and cytogenetic techniques were used to characterise a novel chromosomal anomaly associated with gonadal dysgenesis. A healthy non-dysmorphic 23 year-old phenotypic female with primary amenorrhea and infertility presented for reproductive endocrinology evaluation. No discrete ovarian tissue was identified on transvaginal ultrasound, although the uterus appeared essentially normal. BMI was 19 kg/m2. Serum FSH and oestradiol were 111 mIU/ml and 15 pmol/l, respectively. TSH, prolactin and all infectious serologies were all normal. The karyotype of 46,X,der(X)t(X;6)(q22;p23) was determined following cytogenetic analysis of peripheral blood lymphocytes via fluorescence in situ hybridisation (FISH) with whole chromosome paint for chromosome 6, and a separate FISH analysis using a 6p subtelomeric probe. The patient was continued on hormone replacement therapy and underwent genetic counselling; the patient subsequently enrolled as a recipient in an anonymous donor oocyte IVF treatment. Translocations involving autosomes and chromosome X are rare. While female carriers of balanced X;autosome translocations are generally phenotypically normal, the impact of unbalanced X;autosome translocations can be severe. This is the first known report of an unbalanced translocation involving X;6. This abnormality was associated with ovarian dysgenesis, but an otherwise normal female phenotype. From this investigation, the observed developmental impact of the unbalanced translocation with breakpoints at Xq22 and 6p23 appears to be limited to ovarian failure.