TY - JOUR
T1 - Identification of copy number variants associated with BPES-like phenotypes
AU - Gijsbers, Antoinet C. J.
AU - D'haene, Barbara
AU - Hilhorst-Hofstee, Yvonne
AU - Mannens, Marcel
AU - Albrecht, Beate
AU - Seidel, Joerg
AU - Witt, David R.
AU - Maisenbacher, Melissa K.
AU - Loeys, Bart
AU - van Essen, Ton
AU - Bakker, Egbert
AU - Hennekam, Raoul
AU - Breuning, Martijn H.
AU - de Baere, Elfride
AU - Ruivenkamp, Claudia A. L.
PY - 2008
Y1 - 2008
N2 - 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
AB - 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
U2 - https://doi.org/10.1007/s00439-008-0574-9
DO - https://doi.org/10.1007/s00439-008-0574-9
M3 - Article
C2 - 18953567
SN - 0340-6717
VL - 124
SP - 489
EP - 498
JO - Human genetics
JF - Human genetics
IS - 5
ER -