Premature ovarian insufficiency as a variable feature of blepharophimosis, ptosis, and epicanthus inversus syndrome associated with c.223C > T p.(Leu75Phe)FOXL2 mutation: a case report.
Special attention is paid to FOXL2 whose mutations are responsible for the blepharophimosis syndrome, often associated with female infertility, and for cancer.
This study highlights the importance of early recognition of BPES and emphasizes the need of personalized therapy and follow-up in female patients carrying distinct FOXL2 mutations.
Several breakpoints nearing FOXL2 (0 Mb to 1.2 Mb, several of which were distant from the 7.4 kb sequence disruption) have been mapped or deduced through a traditional method in BPES patients with chromosome reciprocal translocation.
A novel insertion in the forkhead transcription factor 2 (FOXL2) was identified in a Chilean patient with blepharophimosis, ptosis, and epicanthus inversus syndrome associated with premature ovarian failure (BPES type I).
Thus, decreased apoptotic and antiproliferative activities caused by mutant forms of FOXL2 found in BPES patients may at least partially contribute to the pathophysiology of ovarian dysfunction.
This is the first study demonstrating a severe BPES phenotype resulting from a FOXL2 missense mutation outside the forkhead domain, expanding our knowledge about the phenotypic consequences of missense mutations outside the forkhead domain in BPES.
Here, we report 1 novel duplication mutation of the FOXL2 gene identified in a large Chinese family affected by type II BPES and 1 less recurrent 17-bp duplication in a large Chinese family affected by BPES of an undetermined type.
Our genotype-phenotype data can be useful for providing a prognosis (i.e. occurrence of associated features) in newborns with BPES carrying a FOXL2 deletion.
The results came back with no novel mutations but one common 30 bp duplication within FOXL2 polyalanine tract in the abovementioned POF plus BPES patient, suggesting mutations in FOXL2 gene was not common among Chinese patients with POF.