Moreover, a higher prevalence of the C allele of a single nucleotide polymorphism (129C-->T), located in the 5'-UTR of the INHalpha gene, was observed in POF patients (80.3%) than in the control group (66.7%) (Fisher's exact test, P = 0.014).
In a Slovenian POF patient, a novel 30 bp deletion was identified that was predicted to remove 10 out of 14 alanines (A221_A230del), from the polyalanine tract downstream of the winged helix/forkhead domain of the FOXL2 protein.
The analysis did not reveal any mutation in the 240 analysed chromosomes, indicating that mutations in the FOXL2 coding region are rarely associated with non-syndromic POF.
This study supports the hypothesis that the INHA 769G>A variant may increase susceptibility to POF with impaired inhibin B bioactivity and provides insight into the complex aetiology of POF.
The Human FOXL2 Mutation Database was created to provide a unique publicly available online resource of information about human FOXL2 mutations/variants associated with BPES and POF.
Sequence analysis of the INHA promoter in 50 POF patients and 50 controls identified a highly polymorphic imperfect TG repeat at approximately -300 bp, that consisted of four common haplotypes (A, B, C and D).
At a repeat in a promoter of the estrogen receptor alpha(ESR1) gene, POF patients had fewer (<18) short repeat alleles than did controls (P=.004 vs. combined controls).
Significant reductions in allele frequency were observed for the -16T allele (New Zealand POF) and -124G allele (total POF) and for INHA promoter haplotypes C (New Zealand POF) and D (Slovenian POF).
The results suggest that short CAG repeats with a relatively high androgen receptor function may constitute a susceptibility factor for the development of POF.
Another POF patient of African origin showed a homozygous nucleotide change in the tenth of DMC1 gene that led to an alteration of the amino acid composition of the protein (M200V).
A single heterozygous missense mutation, substitution of a cytosine residue with thymidine in exon 2 of MSH5, was found in two Caucasian women in whom POF developed at 18 and 36 years of age.