This study demonstrates the importance of cascade screening and provides new information on inheritance and parental mosaicism in BPES which will aid genetic counselling and accurate risk management.
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).
Our data provide evidence in favour of the implication of FOXL2 variants in non-syndromic POF and confirm the regulatory interaction between FOXL2 and OSR2 whose perturbation might contribute to the palpebral abnormalities observed in BPES patients.
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.