ABSTRACT
Mutations in FOXL2, a forkhead transcription factor gene, have recently been shown to cause blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) types I and II, a rare genetic disorder. In BPES type I a complex eyelid malformation is associated with premature ovarian failure (POF), whereas in BPES type II the eyelid defect occurs as an isolated entity. In this study, we describe the identification of novel mutations in the FOXL2 gene in BPES types I and II families, in sporadic BPES patients, and in BPES families where the type could not be established. In 67% of the patients studied, we identified a mutation in the FOXL2 gene. In total, 21 mutations (17 of which are novel) and one microdeletion were identified. Thirteen of these FOXL2 mutations are unique. In this study, we demonstrate that there is a genotype--phenotype correlation for either types of BPES by the finding that mutations predicted to result in a truncated protein either lacking or containing the forkhead domain lead to BPES type I. In contrast, duplications within or downstream of the forkhead domain, and a frameshift downstream of them, all predicted to result in an extended protein, cause BPES type II. In addition, in 30 unrelated patients with isolated POF no causal mutations were identified in FOXL2. Our study provides further evidence that FOXL2 haploinsufficiency may cause BPES types I and II by the effect of a null allele and a hypomorphic allele, respectively. Furthermore, we propose that in a fraction of the BPES patients the genetic defect does not reside within the coding region of the FOXL2 gene and may be caused by a position effect.
Subject(s)
Blepharophimosis/diagnosis , Blepharophimosis/genetics , Blepharoptosis/diagnosis , Blepharoptosis/genetics , DNA-Binding Proteins/genetics , Eyelids/abnormalities , Mutation , Transcription Factors/genetics , Alleles , Amino Acid Sequence , Base Sequence , Family Health , Female , Forkhead Box Protein L2 , Forkhead Transcription Factors , Frameshift Mutation , Gene Deletion , Genotype , Humans , In Situ Hybridization, Fluorescence , Male , Models, Genetic , Molecular Sequence Data , Mutation, Missense , Pedigree , Phenotype , SyndromeABSTRACT
Methylobacterium sp. ZP24, isolated from a local pond, is able to grow in a medium containing 12 g l-1 lactose as a sole source of carbon, giving 5.25 g l-1 biomass yield and poly-3-hydroxybutyrate (PHB) up to 59% of its dry weight in 40 h. The isolate was also able to utilize cheese whey and produce 1.1 g l-1 PHB. Addition of ammonium sulphate increased the production of PHB from whey 2.5-fold. The potential of Methylobacterium sp. ZP24 in PHB production from cheese whey is discussed.
