Abstract
BackgroundBlepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is a rare autosomal dominant disease. Mutations in the forkhead box L2 (FOXL2) gene cause two types of BPES distinguished by the presence (type I) and absence (type II) of premature ovarian failure (POF). The purpose of this study was to identify possible mutations in FOXL2 in two Chinese families with BPES.MethodsTwo large autosomal dominant Chinese BPES families were enrolled in this study. Genomic DNA was obtained from the leukocytes in peripheral venous blood. Four overlapping sets of primers were used to amplify the entire coding region and nearby intron sequences of the FOXL2 gene for mutations detection using polymerase chain reaction (PCR) and sequencing analyses. The sequencing results were analyzed using DNAstar software.ResultsAll patients of the two families demonstrated typical features of BPES type II, including small palpebral fissures, ptosis, telecanthus, and epicanthus inversus without female infertility (POF). A novel FOXL2 heterozygous indel mutation c.675_690delinsT, including a 16-bp deletion and a 1-bp(T) insertion (p.Ala226_Ala230del), which would result in deletion of 5 alanine residues of a poly-alanine (poly-Ala) tract in the protein, was identified in all affected members of family A. A novel heterozygous missense mutation (c.223C > T, p.Leu75Phe) was identified in family B.ConclusionsTwo novel FOXL2 mutations were identified in Chinese families with BPES. Our results expand the spectrum of FOXL2 mutations and provide additional structure-function insights into the FOXL2 protein.
Highlights
Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is a rare autosomal dominant disease
Depending on the presence or absence of premature ovarian failure (POF), BPES has been divided into two subsets: type I is characterized by eyelid malformation and female infertility through POF, and type II is characterized by eyelid malformation [2]
It is the first report that a partial deletion of the poly-Ala tract in forkhead box L2 (FOXL2) is associated with BPES type II, but the other poly-Ala tract partial deletion (p.Ala221_Ala230del) has been described in one POF patient with no eye defects [25]
Summary
Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is a rare autosomal dominant disease. Mutations in the forkhead box L2 (FOXL2) gene cause two types of BPES distinguished by the presence (type I) and absence (type II) of premature ovarian failure (POF). Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES; OMIM# 110100) is an autosomal dominant developmental disorder characterized by a malformation of the eyelids. It has a prevalence of approximately 1 in 50,000 [1]. Depending on the presence or absence of premature ovarian failure (POF), BPES has been divided into two subsets: type I is characterized by eyelid malformation and female infertility through POF, and type II is characterized by eyelid malformation [2]. Expression studies have revealed that the FOXL2 protein is present in the mesenchyme of developing eyelids, in fetal and adult granulosa cells of the ovary, and in the embryonic and adult gonadotropic cells of the anterior pituitary [8,9,10,11,12], suggesting that this protein might play a key role in regulating the early development of the eyelids and ovaries and maintaining the female gonads in vertebrate species [8, 10]
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