1. Identification of copy number variants associated with BPES-like phenotypes
- Author
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Raoul C.M. Hennekam, Claudia A. L. Ruivenkamp, Joerg Seidel, Yvonne Hilhorst-Hofstee, Egbert Bakker, Ton van Essen, Elfride De Baere, Beate Albrecht, Melissa K. Maisenbacher, Martijn H. Breuning, Antoinet C.J. Gijsbers, Barbara D'haene, Marcel M.A.M. Mannens, Bart Loeys, David R. Witt, Amsterdam Cardiovascular Sciences, Amsterdam Reproduction & Development (AR&D), Human Genetics, Amsterdam Neuroscience, Amsterdam Public Health, and Paediatric Genetics
- Subjects
Male ,FOXL2 ,Gene Dosage ,Telecanthus ,Biology ,Bioinformatics ,Polymorphism, Single Nucleotide ,PATIENT ,BLEPHAROPHIMOSIS ,Intellectual Disability ,medicine ,Genetics ,Blepharoptosis ,Humans ,MALFORMATIONS ,Genetics(clinical) ,Copy-number variation ,TRISOMY ,Genetics (clinical) ,In Situ Hybridization, Fluorescence ,Chromosome Aberrations ,Psychomotor retardation ,INVERSUS SYNDROME ,REARRANGEMENTS ,Eyelids ,Genetic Variation ,Syndrome ,medicine.disease ,Phenotype ,Blepharophimosis ,Human genetics ,Premature ovarian failure ,Pedigree ,DELETIONS ,DEL(18)(Q12.2Q21.1) ,Female ,medicine.symptom ,Trisomy ,MENTAL-RETARDATION - Abstract
Blepharophimosis-Ptosis-Epicanthus inversus syndrome (BPES) is a well-characterized rare syndrome that includes an eyelid malformation associated with (type I) or without premature ovarian failure (type II). Patients with typical BPES have four major characteristics: blepharophimosis, ptosis, epicanthus inversus and telecanthus. Mutations in the FOXL2 gene, encoding a forkhead transcription factor, are responsible for the majority of both types of BPES. However, many patients with BPES-like features, i.e., having at least two major characteristics of BPES, have an unidentified cause. Here, we report on a group of 27 patients with BPES-like features, but without an identified genetic defect in the FOXL2 gene or flanking region. These patients were analyzed with whole-genome high-density arrays in order to identify copy number variants (CNVs) that might explain the BPES-like phenotype. In nine out of 27 patients (33%) CNVs not previously described as polymorphisms were detected. Four of these patients displayed psychomotor retardation as an additional clinical characteristic. In conclusion, we demonstrate that BPES-like phenotypes are frequently caused by CNVs, and we emphasize the importance of whole-genome copy number screening to identify the underlying genetic causes of these phenotypes.
- Published
- 2008
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