Premature ovarian failure is clearly a heterogeneous disorder. The terms 'hypergonadotropic ovarian failure' and 'hypergonadotropic ovarian dysgenesis' (see ODG1, 233300) have been used to indicate a group of disorders in which amenorrhea associated with elevated levels of serum ... Premature ovarian failure is clearly a heterogeneous disorder. The terms 'hypergonadotropic ovarian failure' and 'hypergonadotropic ovarian dysgenesis' (see ODG1, 233300) have been used to indicate a group of disorders in which amenorrhea associated with elevated levels of serum gonadotropins occurs long before the age of 40 years (Coulam, 1982). Cytogenetic studies of X-chromosome aberrations have suggested that it is mainly the long arm of the X chromosome that is involved in defects of ovulation (Bione et al., 1998). - Genetic Heterogeneity of Premature Ovarian Failure Mutations in genes identified within a region defined as POF2 (Xq13.3-q21.1) have been found to cause other forms of POF: POF2A (300511) by mutation in the DIAPH2 gene (300108) and POF2B (300604) by mutation in the POF1B gene (300603). See also POF3 (608996), which can be caused by mutation in the FOXL2 gene (605597), POF4 (see 300510), which can be caused by mutation in the BMP15 gene (300247), POF5 (611548), which can be caused by mutation in the NOBOX gene (610934), POF6 (612310), which can be caused by mutation in the FIGLA gene (608697), and POF7 (612964), which is caused by mutation in the NR5A1 gene (184757).
Although the average age of menarche decreased during the 20th century, the mean age of menopause appears to be invariant with time and race and occurs at approximately 50 years. Premature ovarian failure can be defined as secondary ... Although the average age of menarche decreased during the 20th century, the mean age of menopause appears to be invariant with time and race and occurs at approximately 50 years. Premature ovarian failure can be defined as secondary amenorrhea with elevated gonadotropins occurring before age 40. Depletion of ova is usually the basis although an ovary no longer sensitive to gonadotropins can masquerade as true failure (Jones and DeMoraes-Ruehsen, 1969; Maxson and Wentz, 1983). Premature ovarian failure is usually idiopathic but occasionally can be due to a genetic disorder that is associated with rapid atresia of follicles, such as Turner variants (Fitch et al., 1982), or with formation of a small number of follicles, as in galactosemia (230400) (Kaufman et al., 1981). Destruction of germ cells in pre- or postpubertal stages by viral infections, drugs (cigarette smoking, antitumor drugs), or radiation can also be responsible. Autoimmunity appears to be the basis of POF in patients with antiovarian antibodies, in Addison disease (240200) and in myasthenia gravis (254200). The role of familial factors was suggested by DeMoraes-Ruehsen and Jones (1967) and by Smith et al. (1979). On the basis of 5 kindreds, Mattison et al. (1984) proposed that POF can be a mendelian disorder, inherited either paternally or maternally, as an autosomal or X-linked dominant. Smith et al. (2004) studied 65 patients with POF and 36 age-matched healthy controls. They found that women with POF were more likely to exhibit ocular surface damage and symptoms of dry eye than age-matched controls, but were not more likely to have reduced tear production. Eggermann et al. (2005) described a 33-year-old German woman with POF and her mother, who both showed mild Turner stigmata including a low-set hairline, moderately high-arched palate, short and mildly webbed neck, and hypoplastic and/or upturned fingernails and toenails. The daughter also had sparse hair and an asymmetric right hypoplastic breast.
Murray et al. (1999) screened a cohort of 209 women with POF for FMR1 premutations and found that 9 had greater than 50 trinucleotide repeats (309550.0004). In addition, they screened this cohort for mutations in FRAXE (309548) and ... Murray et al. (1999) screened a cohort of 209 women with POF for FMR1 premutations and found that 9 had greater than 50 trinucleotide repeats (309550.0004). In addition, they screened this cohort for mutations in FRAXE (309548) and found an excess of FRAXE alleles with fewer than 11 repeats. Sequence analysis of these alleles showed that the excess was caused by 3 individuals carrying cryptic deletions in FMR2, the gene associated with FRAXE. Murray et al. (1999) proposed that microdeletions in FMR2 may be a significant cause of POF, being found in 1.5% of the population with POF, but in only 0.04% of the general population.