The clinical presentation of these patients has clear similarities with previously reported cases with a terminal 1q deletion. Corpus callosum abnormalities were present in 10 of our patients. The AKT3 gene has been reported as an important candidate gene causing this abnormality. However, through detailed molecular analysis of the deletion sizes in our patient cohort, we were able to delineate the critical region for corpus callosum abnormalities to a 360 kb genomic segment which contains four possible candidate genes, but excluding the AKT3 gene.

Cell division serves to distribute chromosomes and organelles into two daughter cells, but the mechanism of rough endoplasmic reticulum (RER) segregation in animal cell mitosis is poorly understood. Here we study the distribution of RER in mitotic HeLa cells and its relation to the cytoskeleton. At metaphase, the RER was located in the cell cortex and was most concentrated in two locations. Close to the plasma membrane the RER was closely associated with cortical actin, and after treatment with Latrunculin A RER elements retracted to the deep cortex and became more tubular. Positioning was therefore dependent on cortical F-actin. Deeper in the cortex cisternae were wrapped tightly around the contours of the spindle body and orientated along microtubules close the spindle poles.Stereology revealed a close correlation between RER volume and cell volume in telophase daughter cells. These results suggest that the RER is positioned at the outer and inner regions of metaphase cortex by association with cytoskeleton. This arrangement combined with a disposition in concentric layers, deep to the plasma membrane, appears to distribute the RER evenly in the cortex and may help to couple quantities of RER and cell constituents.

Williams-Beuren syndrome is a well-known microdeletion syndrome with a recognizable clinical phenotype. The subtle phenotype of the reciprocal microduplication of the Williams-Beuren critical region has been described recently. We report seven further patients, and a transmitting parent, with 7q11.23 microduplication. All our patients had speech delay, autistic features and facial dysmorphism consistent with the published literature. We conclude that the presence of specific dysmorphic features, including straight, neat eyebrows, thin lips and a short philtrum, in our patients with speech delay and autistic features provides further evidence that the children with 7q11.23 microduplication have a recognizable phenotype.

The MLL gene, located at 11q23, is frequently rearranged in acute leukaemia as either chimaeric fusion genes or partial tandem duplications. We report a series of 12 acute leukaemia cases with apparent amplification of the MLL gene ascertained using fluorescence in situ hybridisation (FISH). Seven cases showed intrachromosomal amplification of MLL, four cases showed extrachromosomal amplification as double minute chromosomes (dmin) and one case had separate subclones with dmin and homogenously staining region (hsr). Southern blot analysis of the MLL gene showed MLL gene rearrangement in three of the 10 successful cases. These cases do not naturally fall into either of the two recognised categories of MLL rearrangement and may represent a third variety of MLL gene abnormalities.

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In the presence of a fetal structural anomaly, fetal DNA can be obtained through invasive testing (e.g. amniocentesis and chorionic villus sampling) in order to undertake genomic testing to attempt to uncover a unifying genetic diagnosis. There are number of traditional and more novel genomic tests available, which can identify aneuploidy, chromosomal structural variation and/or sequence variants within genes. The cumulative diagnostic yield of such technologies is approximately 25%, 6% and up to 80% in some cohorts for QF-PCR/G-banding karyotype, chromosome microarray and exome sequencing, respectively. Learning objectivesTo understand the technical basis and clinical indications for QF-PCR, G-banding karyotype, chromosome microarray and exome sequencing.To appreciate the potential benefits and challenges associated with exome sequencing. To gain awareness of modern technologies that may be utilised to address recurrence risk, e.g. preimplantation genetic diagnosis and non-invasive prenatal diagnosis. Ethical issuesNot all technologies are currently available across all four nations of the UK, hence challenges are raised regarding healthcare equity. There can be uncertainty around the interpretation of prenatal genomic test results, which can have implications in counselling, particularly regarding termination of pregnancy. Incidental findings may be revealed, which can have implications for counselling and the future health of the fetus and the parents.