Ovarian Dysgenesis 3

A number sign (#) is used with this entry because this form of hypergonadotropic ovarian dysgenesis (ODG3) is caused by homozygous mutation in the PSMC3IP gene (608665) on chromosome 17q12-q21.

For a discussion of genetic heterogeneity of hypergonadotropic ovarian dysgenesis, see ODG1 (233300).

Clinical Features

Zangen et al. (2011) studied a large consanguineous Arab Palestinian pedigree in which at least 5 females were affected with complete XX gonadal dysgenesis. The proband failed to develop spontaneous puberty and at 15 years of age, breast development and pubic hair were at Tanner stage 1 and 2, respectively; hormonal testing revealed high basal gonadotropin levels with undetectable estradiol and progesterone and normal levels of androgens. Her karyotype was 46,XX with no SRY sequence detected, and abdominal ultrasound and MRI showed uterine hypoplasia and undetectable ovaries. An older sister and a second cousin also presented with primary amenorrhea, at 18 and 17 years of age, respectively, and had laboratory and imaging results similar to those of the proband. In addition, 2 female cousins of the proband's father, who were both in their sixth decade and childless, had primary amenorrhea; in both cases, karyotype was 46,XX and abdominal ultrasounds showed hypoplastic uterus and undetectable ovaries.

Mapping

In a large consanguineous Arab Palestinian pedigree with hypergonadotropic ovarian dysgenesis, Zangen et al. (2011) performed homozygosity mapping and identified a 4.5-Mb region on chromosome 17 (Chr17: 40,174,841-44,708,028, GRCh37) that fulfilled homozygosity criteria.

Molecular Genetics

In a large consanguineous Arab Palestinian pedigree with hypergonadotropic ovarian dysgenesis mapping to chromosome 17, Zangen et al. (2011) analyzed candidate genes and identified homozygosity for a 3-bp deletion in the PSMC3IP gene (608665.0001) that segregated with disease in the family and was not found in 254 ethnically matched control chromosomes.