Our study suggests that a homozygous point mutation in POF1B influences the pathogenesis of POF by altering POF1B binding to nonmuscle actin filaments.
FOXL2 is a forkhead transcription factor, essential for ovarian function, whose mutations are responsible for the blepharophimosis syndrome, characterized by craniofacial defects, often associated with premature ovarian failure.
Genetic analysis of the FMR1 gene in over three generations of females revealed that six carried pre-mutated alleles (61-200), of which two were also affected by POF.
Autosomal disorders such as mutations of the phosphomannomutase 2 (PMM2) gene, the galactose-1-phosphate uridyltransferase (GALT) gene, the FSH receptor (FSHR) gene, chromosome 3q containing the Blepharophimosis gene and the autoimmune regulator (AIRE) gene, responsible for polyendocrinopathy-candidiasis-ectodermal dystrophy, have been identified in patients with POF.
Mutations in NR5A1 were first described in patients with primary adrenal insufficiency and 46,XY disorders of sexual development and later also in men with hypospadias, bilateral anorchia and micropenis and women with primary ovarian insufficiency.
To date, mutations associated with POF have been identified in a small number of genes, including those encoding inhibin alpha (INHA), the FSH receptor and the LH/chorio gonadotrophin receptor.
To assess whether the number of triple CGG expansion of the FMR1 (fragile X) gene, known to correlate at premutation (55-200 repeats) and full mutation (>200 repeats) ranges with risk toward premature ovarian failure (POF), also correlates with milder forms of premature ovarian senescence.
FOXL2 is a gene encoding a forkhead transcription factor, whose mutations are responsible for the blepharophimosis-ptosis-epicanthus inversus syndrome that often involves premature ovarian failure.
However, three single nucleotide polymorphisms in the BMP15 gene, two in the 5' untranslated region (31T>G and 71C>G) and another in exon 1 (387G>A), were found to be common in both POF and control groups.
Mutations in FOXL2 are known to cause autosomal dominant blepharophimosis-ptosis-epicanthus inversus syndrome (BPES), variably associated with premature ovarian failure.
Inactivating mutations of FSH receptor are associated with partial to complete premature ovarian failure in women and variable impairment of spermatogenesis and small testes in men.
Based on the current evidence, we concluded that intermediate-sized FMR1 CGG repeat alleles should not be considered as a high-risk factor for POF and DOR.
The tight junction localisation was maintained by the human POF1B stably expressed in the MDCK polarised epithelial cell line, whereas it was lost by the POF1BR329Q variant associated with POF.