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The Xq25 duplications syndrome has recently emerged as a distinct clinical entity. We report here on six new patients belonging to two unrelated families and harbouring an Xq25 microduplication detected by array CGH. Similarly to previously reported cases, the phenotype of our patients is characterized by delayed milestones, speech disturbance, intellectual disability, abnormal behaviours and a characteristic facial dysmorphism. The common duplicated interval allowed further refinement of the shortest region of overlap to 173 kb, including only one gene, STAG2, which encodes a component of the cohesin complex. We suggest that increased STAG2 gene copy number and dysregulation of its downstream target genes may be responsible for the specific clinical findings of this syndrome. Therefore, the Xq25 microduplication could be considered as a novel cohesinopathy, thus increasing the group of these disorders.

Although discordant phenotypes in monozygotic twins with developmental disorder are not an exception, underlying genetic discordance is rarely reported. Here, we report on the clinical and cytogenetic details of 4-year-old female monozygotic twins with discordant phenotypes. Twin 1 exhibited global developmental delay, overweight and hyperactivity. Twin 2 had an autistic spectrum disorder. Molecular karyotyping in twin 1 identified a 2p25.3 deletion, further confirmed by Fluorescence in situ hybridization (FISH) analysis on leukocytes. Interestingly, array comparative genomic hybridization was normal in twin 2 but FISH analysis using the same probe as twin 1 showed mosaicism with one-third of cells with a 2p25.3 deletion, one-third of cells with a 2p25.3 duplication, and one-third of normal cells. Genotyping with microsatellite markers confirmed the monozygosity of the twins. We propose that the chromosome imbalance may be due to a mitotic non-allelic recombination occurring during blastomeric divisions of a normal zygote. Such event will result in three distinct cell populations, whose proportion in each embryo formed after separation from the zygote may differ, leading to discordant chromosomal anomalies between twins. We also discuss that the MYTL1L and the SNTG2 genes within the reported region could probably relate to the phenotypic discordance of the monozygotic twins.

Four cases of partial trisomy 18q are reported and compared to observations from the literature. The phenotype of 18qter trisomy is described and compared to full trisomy 18.

Three patients (two females, one male) are reported with bilateral aniridia, Wilms' tumor, more or less moderate mental retardation, decreased catalase activity, and del 1 lp13. These and 34 case reports from the literature are discussed with respect to: sex ratio, maternal age, type of chromosomal imbalance and frequency of associated rearrangements, prevalence of aniridia and other eye disorders, predisposition to tumor development, genitourinary anomalies, growth and mental retardation, and catalase involvement. Possible gene relationship within the complex locus and with neighbouring 1 lp genes is discussed.

The finding of a mixture of 46,XX and 46,XY cells in an individual has been rarely reported in literature. It usually results in individuals with ambiguous genitalia. Approximately 10% of true human hermaphrodites show this type of karyotype. However, the underlying mechanisms are poorly understood. It may be the result of mosaicism or chimerism. By definition, a chimera is produced by the fusion of two different zygotes in a single embryo, while a mosaic contains genetically different cells issued from a single zygote. Several mechanisms are involved in the production of chimera. Stricto sensu, chimerism occurs from the post-zygotic fusion of two distinct embryos leading to a tetragametic chimera. In addition, there are other entities, which are also referred to as chimera: parthenogenetic chimera and chimera resulting from fertilization of the second polar body. Furthermore, a particular type of chimera called 'androgenetic chimera' recently described in fetuses with placental mesenchymal dysplasia and in rare patients with Beckwith-Wiedemann syndrome is discussed. Strategies to study mechanisms leading to the production of chimera and mosaics are also proposed.

CHARGE association is a non-random occurrence of congenital malformations including coloboma, heart disease, choanal atresia, retarded growth and/or retarded development, genital hypoplasia, ear anomalies and/or deafness. The cause of this association remains unknown. Various genetic mechanisms have been proposed, including a contiguous gene syndrome but, so far, no recurrent locus has been identified. To address this question, we decided to perform a comparative genomic hybridization (CGH) study on a cohort of 27 patients with CHARGE association and a normal standard karyotype. We found two chromosomal anomalies: a der(9)t(9;13) derived from a paternal translocation and a der(6)t(4;6) of unknown origin. This suggests that chromosome imbalances may well mimic CHARGE association. Therefore patients with CHARGE association must be carefully tested with classical and molecular cytogenetic techniques to detect a potential chromosome imbalance. It is expected that more stringent diagnostic criteria of CHARGE association could define a more homogeneous group of patients where a single genetic cause might be identified.

Segmental aneusomy for small chromosomal regions has been shown to be a common cause of mental retardation and multiple congenital anomalies. A screening method for such chromosome aberrations that are not detected using standard cytogenetic techniques is needed. Recent studies have focused on detection of subtle terminal chromosome aberrations using subtelomeric probes. This approach however excludes significant regions of the genome where submicroscopic rearrangements are also liable to occur. The aim of the present study was to evaluate the efficiency of comparative genomic hybridisation (CGH) for screening of submicroscopic chromosomal rearrangements. CGH was performed in a cohort of 17 patients (14 families) with mental retardation, dysmorphic features and a normal karyotype. Five subtle unbalanced rearrangements were identified in 7 patients. Subsequent FISH studies confirmed these results. Although no interstitial submicroscopic rearrangement was detected in this small series, the study emphasises the value of CGH as a screening approach to detect subtle chromosome rearrangements in mentally retarded patients with dysmorphic features and a normal karyotype.

A female infant with a de novo del 6q14q16.2 and five other patients with del 6q1 reported in the literature allow the delineation of a characteristic syndrome, the main features of which are: severe mental retardation, a round face with full cheeks, upslanting palpebral fissures, a short neck, umbilical hernia, malpositioned feet with syndactyly II-III, and typical dermatoglyphics with an excess of whorls and clinodactyly of the Vth finger.