Ophthalmic Genet

We report on a young female patient with the clinical features of blepharophimosis-ptosis-epicanthus inversus syndrome (BPES, OMIM 110100) and a balanced chromosome translocation 46, XX, t(2;3)(q33;q23)dn.BPES is a rare autosomal dominant congenital disorder characterized by the eponymous oculo-facial features that are, in female patients, associated either with (type 1 BPES) or without (type 2 BPES) premature ovarian failure. Both types of BPES are caused by heterozygous mutations in the FOXL2 gene, which is located in chromosome band 3q23. Chromosome aberrations such as balanced rearrangements have only rarely been observed in BPES patients but can provide valuable information about regulatory regions of FOXL2. The translocation in this patient broadens our knowledge of pathogenic mechanisms in BPES and highlights the importance of conventional cytogenetic investigations in patients with negative results of FOXL2 mutation screening as a prerequisite for optimal management and genetic counseling

Am J Med Genet A

Deletions of chromosome bands 13q33-34 are rare. Patients with such deletions have mental retardation, microcephaly, and distinct facial features. Male patients frequently also have genital malformations. We report on four patients with three overlapping deletions of 13q33-34 that have been characterized by tiling-path array-CGH. Patient 1 had mental retardation and microcephaly with an interstitial 4.7 Mb deletion and a translocation t(12;13)(q13.3;q32.3). His mother (Patient 2), who also had mental retardation and microcephaly, carried the identical chromosome aberration. Patient 3 was a girl with a de novo insertion ins(7;13)(p15.1;q22q31) and interstitial 4.5 Mb deletion in 13q33-34. She had mental retardation and microcephaly. Patient 4 was a newborn boy with severe genital malformation (penoscrotal transposition and hypospadias) and microcephaly. He had a de novo ring chromosome 13 lacking the terminal 9.3 Mb of 13q. Karyotype-phenotype comparisons of these and eight previously published del13q33-34 patients suggest EFNB2 as a candidate gene for genital malformations in males. Molecular cytogenetic definition of a common deleted region in all patients suggests ARHGEF7 as a candidate gene for mental retardation and microcephaly