Does the X-Autosome translocation affect the normal ovarian development?

GRACIELA DEL REY; MARÍA EUGENIA ESCOBAR; MARCELA LESCANO; JUDITH MINCMAN; IRMA COCO; ADRIANA BOYWITT; RODOLFO DE BELLIS; ROBERTO COCO

New York, N.Y., USA

Congreso; LWPES/ESPE 8th Joint Meeting; 2009

APEG,APPES,JSPE and SLEP

Premature ovarian failure (POF) is characterized by hypergonadotropic hypogonadism and amenorrhea for more than 6 months before the age of 40. Chromosomal rearrangements of the Xq chromosome as deletions or X-autosome translocation are associated with POF. A critical region for normal ovarian function has been proposed for Xq13-q26. Within this zone the most frequent breakpoints involve two specific regions associated with POF: POF1 located in Xq26-qter and POF2 in Xq13.3-q21.1. We identified two balanced X-autosome translocations by high resolution cytogenetics methods in a female affected with POF and in a girl with growth retardation and in her carrier mother with the same karyotype and POF.Patient 1: 19 years old with primary amenorrhea. Karyotype: 46,X,t(X;11)(q21;q21). After 3 years of estrogen and progesterone replacement therapy she had spontaneous pregnancy and delivered normal girl.Patient 2: 9 years old. Height: below Pc3. Without hormone therapy she started breast development at 10.6 years old. Menarche: 11.5 years old with regular menses until now (at 12.5 years). Karyotype: 46,X,t(X;10)(q26.1;q26.2) inherited from her carrier mother. She had two normal brothers, one of them carried the apparent balanced translocation. Mother: Height: Pc3-10. Menarche at the age of 12 with normal menses. At the age 35 she began with irregular cycles and entered in menopause at 40 years. She had an infertile sister.Fluorescence in situ hybridation (FISH) using the whole X chromosome painting probe analysis in the metaphases of the patient confirmed complete hybridization on normal and translocated X chromosomes. Molecular studies were performed in the mother and her daughter to study the triplet (CGG)n of FMR1 gene (Xq27.3) and the STRs of DXS1205 (Xq27.2), DXS1091 (Xq28) and DXS8069 (Xq28) linked to POF1 region. The results were normal amplification of CGG triplet and revealed two alleles. The STR of DXS1205 evidenced only one allele while the remains STRs showed two alleles. We conclude that different breakpoints on Xq critical region not always affect the genes involved in ovarian development. POF could be caused by haploinsufficiency of some genes, a position effect on the autosome translocated on Xq or by asinapsis during meiosis which leads to apoptosis of germ cells in the ovary, essential for the development of ovarian follicles.