title: Intragenic and extragenic disruptions of FOXL2 mapped by whole genome low-coverage sequencing in two BPES families with chromosome reciprocal translocation.
abstract: Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is a rare autosomal dominant disorder that affects craniofacial development and ovarian function. FOXL2 is the only gene known to be responsible for BPES. The majority of BPES patients show intragenic mutations of FOXL2. Recently, a 7.4 kb sequence disruption, which was 283 kb upstream of FOXL2, was identified to independently contribute to the BPES phenotype. 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. In this study, two BPES families with chromosome reciprocal translocation were investigated. Intragenic mutations of FOXL2 or pathogenic copy number variations were excluded for the two BPES families. All of the four breakpoints were identified at a base-precise manner using Giemsa banding and whole genome low-coverage sequencing (WGLCS). In family 01, the breakpoints were found at chr1:95,609,998 and chr3:138,879, 114 (213,132 bp upstream of FOXL2). In family 02, the breakpoints were located at chr3:138,665,431 (intragenic disruptions of FOXL2) and chr20:56,924,609. Results indicate that the intragenic and extragenic interruptions of FOXL2 can be accurately and rapidly detected using WGLCS. In addition, both the 213 kb upstream and intragenic interruptions of FOXL2 can cause BPES phenotype.
authors.affiliation: The Lab. of Genetics and Metabolism, Hunan Children's Research Institute (HCRI), Hunan Children's Hospital, The Paediatric Academy of University of South China, Changsha, China. Electronic address: yongjia727@aliyun.com.
authors.forename: Yongjia
authors.initials: Y
authors.lastname: Yang
authors.affiliation: The Lab. of Genetics and Metabolism, Hunan Children's Research Institute (HCRI), Hunan Children's Hospital, The Paediatric Academy of University of South China, Changsha, China; BGI-Shenzhen, Shenzhen, China.
authors.forename: Chuanchun
authors.initials: C
authors.lastname: Yang
authors.affiliation: The Lab. of Genetics and Metabolism, Hunan Children's Research Institute (HCRI), Hunan Children's Hospital, The Paediatric Academy of University of South China, Changsha, China; The People's Hospital of Hunan Province, Changsha China. Electronic address: xiangeryiym@aliyun.com.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: The Lab. of Genetics and Metabolism, Hunan Children's Research Institute (HCRI), Hunan Children's Hospital, The Paediatric Academy of University of South China, Changsha, China; BGI-Shenzhen, Shenzhen, China.
authors.forename: Haixiao
authors.initials: H
authors.lastname: Chen
authors.affiliation: The Lab. of Genetics and Metabolism, Hunan Children's Research Institute (HCRI), Hunan Children's Hospital, The Paediatric Academy of University of South China, Changsha, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhao
authors.affiliation: The Lab. of Genetics and Metabolism, Hunan Children's Research Institute (HCRI), Hunan Children's Hospital, The Paediatric Academy of University of South China, Changsha, China.
authors.forename: Xinyu
authors.initials: X
authors.lastname: He
authors.affiliation: The Department of Ophthalmology, Hunan Children's Hospital, The Paediatric Academy of University of South China, Changsha, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Tao
authors.affiliation: The Department of Ophthalmology, Hunan Children's Hospital, The Paediatric Academy of University of South China, Changsha, China.
authors.forename: Pin
authors.initials: P
authors.lastname: Wang
authors.affiliation: The Department of Ophthalmology, Hunan Children's Hospital, The Paediatric Academy of University of South China, Changsha, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Zhou
authors.affiliation: The Lab. of Genetics and Metabolism, Hunan Children's Research Institute (HCRI), Hunan Children's Hospital, The Paediatric Academy of University of South China, Changsha, China.
authors.forename: Liu
authors.initials: L
authors.lastname: Zhao
authors.affiliation: The Lab. of Genetics and Metabolism, Hunan Children's Research Institute (HCRI), Hunan Children's Hospital, The Paediatric Academy of University of South China, Changsha, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Tu
authors.affiliation: The Lab. of Genetics and Metabolism, Hunan Children's Research Institute (HCRI), Hunan Children's Hospital, The Paediatric Academy of University of South China, Changsha, China; BGI-Shenzhen, Shenzhen, China.
authors.forename: Zirui
authors.initials: Z
authors.lastname: Dong
authors.affiliation: The Lab. of Genetics and Metabolism, Hunan Children's Research Institute (HCRI), Hunan Children's Hospital, The Paediatric Academy of University of South China, Changsha, China; BGI-Shenzhen, Shenzhen, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.affiliation: Institute of Endocrinology, Second Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Xie
mesh_terms: D001483:Base Sequence; D016569:Blepharophimosis / Q000175:diagnosis / Q000235:genetics*; D002675:Child, Preschool; D056905:Chromosome Breakpoints; D004370:Duane Retraction Syndrome / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors / Q000235:genetics*; D015894:Genome, Human; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D014178:Translocation, Genetic; D014430:Twins, Monozygotic
chemical_list: C421604:FOXL2 protein, human; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors
keywords: BPES; Chromosome reciprocal translocation; FOXL2; Whole genome low-coverage sequencing