Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0002453 (amenorrhea)
 6,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Premature ovarian failure (POF) is an unexplained amenorrhoea (>6 months) with raised levels of gonadotropins (FSH>40 U/L) occurring before the age of 40 years. Recent studies have elucidated the role of oocyte derived growth factors (BMP15 and GDF9) in maintenance of folliculogenesis, granulosa cell (GC) proliferation and overall fertility. Our recently published work showed presence of two rare missense variants in the GDF9 gene associated with ovarian failure (Dixit et al. 2005, Menopause 12:749-754). The present case-control study has been structured to establish the role of BMP15 germline status associated with ovarian failure. Sequence analysis of the coding region of the BMP15 gene was carried out in a cohort of women with POF (n=133), primary amenorrhoea (n=60), and secondary amenorrhoea (n=9) compared with control females (n=197). This study revealed a total of 18 germline variants in the coding region of BMP15 gene, including 16 novel variants. These novel variants include one intronic variant, one 3' flanking variant, one silent variant, and 13 missense variants. Eleven missense variants were present only in cases with complete absence in the control females. The remaining two missense variants viz. c.308A>G (p.Asn103Ser) and c.788_789insTCT (p.Leu263_Arg264insLeu) were present both in the cases and in the controls. The c.788_789insTCT variant was significantly higher in primary amenorrhoea cases than in the controls (Fisher's exact test, P=0.034). Three frequent variants c.-9C>G, c.308A>G, and c.852C>T were chosen for haplotyping. The haplotype G-G-C was found to be significantly associated with ovarian failure (P=0.0075). In a nutshell, the BMP15 gene is highly associated with etiology of ovarian failure.
 ...
PMID:Missense mutations in the BMP15 gene are associated with ovarian failure. 1650 50

Premature ovarian failure (POF) is defined by at least four months of amenorrhea with elevated gonadotropins (usually above 40 UI/L) detected on two occasions a few weeks apart, in a woman before the age of 40. It occurs in 1 out of 10,000 in women below the age of 20, 1/1,000 below 30 and 1% in women before the age of 40. In 80% of POF cases, the etiology is unknown, except for Turner syndrome. The different etiologies identified are 1) iatrogenic following chemotherapy and/or radiotherapy, 2) autoimmune, 3) viral, 4) genetic (RFSH, FOXL2, FRAXA, BMP15, GDF9, GALT, 17 hydroxylase...). Management of these patients includes hormone replacement therapy in order to avoid an increase in cardiovascular risk and osteoporosis related to hypoestrogenism. Infertility is common, as only 3 to 10% of the patients will have natural conception. When fertility is desired, women with POF should be oriented towards oocyte donation centers. Research is currently performed in order to identify new genes involved in POF.
 ...
PMID:[Premature ovarian failure]. 1719 65

Premature ovarian failure (POF) is defined as an amenorrhea for more than 4months, associated with elevated gonadotropins, usually higher than 20mIU/ml, occurring in a woman before the age of 40. Some candidate genes have been identified in the past 15years, such as FOXL2, FSHR, BMP15, GDF9, Xfra premutation. However, POF etiology remains unknown in more than 90% of cases. The first strategy to identify candidate gene, apart from studying genes involved in ovarian failure in animal models, relies on the study of X chromosome deletions and X;autosome translocations in patients. The second strategy is based on linkage analysis, the third one on Comparative Genomic Hybridization (CGH) array. The latest strategy relies on Genome-Wide Association Studies (GWAS). This technique consists in screening single nucleotide polymorphisms (SNPs) in patients and controls. So far, three studies have been performed and have identified different loci potentially linked to POF, such as PTHB1 and ADAMTS19. However, replications in independent cohorts need to be performed. GWAS studies on large cohorts of women with POF should find new candidate genes in the near future.
 ...
PMID:Genome-wide association study and premature ovarian failure. 2036 63

Premature ovarian failure (POF) is unexplained amenorrhoea (>6 months), increased FSH (>20 IU/l) and LH occurring before 40 years. Several genes are reported as having significance in POF, including genes governing regulation of the hypothalamic-pituitary-ovarian axis, but their role in ovarian physiology is not known. Deletions or translocations in Xq arm have been found to be associated with POF, assuming presence of ovarian-related genes but ovary-related function of these genes is unclear. Several researchers have suggested specific loci on Xq critical region, POF1 and POF2 and genes DIA, FMR1 and FMR2. The understanding of ovarian physiology, its regulation and genes involved is important to explain the causes of POF. Some genes coordinate development of germ cell to primordial stage, e.g. GDF9, BMP15 and NGF, while others regulate development of further stages, such as FSH and LH. Mutation in these genes may lead to female infertility and are likely to be candidate genes for POF. Recently, association between blepharophimosis-ptosis-epicanthus inversus syndrome type 1 and POF has emerged as a possibility. Galactosaemia is also shown to be important in POF due to toxic effects of accumulated galactose or downstream products. Thus, understanding the role of several genes can be used for the appropriate genetic diagnosis, research and in the clinical practice of POF.
 ...
PMID:Genes governing premature ovarian failure. 2038 64