Leggett V.,University of Oxford |
Jacobs P.,Wessex Regional Genetics Laboratory |
Nation K.,University of Oxford |
Scerif G.,University of Oxford |
Bishop D.V.M.,University of Oxford
Developmental Medicine and Child Neurology | Year: 2010
Aim: To review systematically the neurodevelopmental characteristics of individuals with sex chromosome trisomies (SCTs). Method: A bibliographic search identified English-language articles on SCTs. The focus was on studies unbiased by clinical referral, with power of at least 0.69 to detect an effect size of 1.0. Results: We identified 35 articles on five neonatally identified samples that had adequate power for our review. An additional 11 studies were included where cases had been identified for reasons other than neurodevelopmental concerns. Individuals with an additional X chromosome had mean IQs that were within broadly normal limits but lower than the respective comparison groups, with verbal IQ most affected. Cognitive outcomes were poorest for females with XXX. Males with XYY had normal-range IQs, but all three SCT groups (XXX, XXY, and XYY) had marked difficulties in speech and language, motor skills, and educational achievement. Nevertheless, most adults with SCTs lived independently. Less evidence was available for brain structure and for attention, social, and psychiatric outcomes. Within each group there was much variation. Interpretation: Individuals with SCTs are at risk of cognitive and behavioural difficulties. However, the evidence base is slender, and further research is needed to ascertain the nature, severity, and causes of these difficulties in unselected samples. © The Authors. Journal compilation © Mac Keith Press 2010.
Jacobs P.A.,Wessex Regional Genetics Laboratory
Annual Review of Genomics and Human Genetics | Year: 2014
This article is one person's view of human cytogenetics over the past 50 years. The flowering of human cytogenetics led the way to the establishment of clinical genetics as one of the most important developments in medicine in the twentieth century. The article is written from the viewpoint of a scientist who never tired of analyzing the images of dividing cells on the light microscope and interpreting the wealth of information contained in them. Copyright © 2014 by Annual Reviews. All rights reserved.
Cohen N.R.,Cellular Pathology |
Hammans S.R.,Wessex Neurological Center |
Macpherson J.,Wessex Regional Genetics Laboratory |
Nicoll J.A.R.,Cellular Pathology |
Nicoll J.A.R.,University of Southampton
Acta Neuropathologica | Year: 2011
Unverricht-Lundborg disease (EPM1A), also known as Baltic myoclonus, is the most common form of progressive myoclonic epilepsy. It is inherited as an auto-somal recessive trait, due to mutations in the Cystatin-B gene promoter region. Although there is much work on rodent models of this disease, there is very little published neuropathology in patients with EPM1A. Here, we present the neuropathology of a patient with genetically confirmed EPM1A, who died at the age of 76. There was atrophy and gliosis affecting predominantly the cerebellum, fronto-temporal cortex, hippocampus and thalamus. We have identified neuronal cytoplasmic inclusions containing the lysosomal proteins, Cathepsin-B and CD68. These inclusions also showed immunopositivity to both TDP-43 and FUS, in some cases associated with an absence of normal neuronal nuclear TDP-43 staining. There were also occasional ubiquitinylated neuronal intranuclear inclusions, some of which were FUS immunopositive. This finding is consistent with neurodegeneration in EPM1A as at least a partial consequence of lysosomal damage to neurons, which have reduced Cystatin-B-related neuroprotection. It also reveals a genetically defined neurodegenerative disease with both FUS and TDP-43 related pathology. © Springer-Verlag 2010.
Crolla J.A.,Wessex Regional Genetics Laboratory |
Wapner R.,Columbia University |
Van Lith J.M.M.,Leiden University
Prenatal Diagnosis | Year: 2014
What's already known about this topic? Chromosomal microarrays (CMA) are routinely used in postnatal genetic diagnosis. CMA is technically applicable in prenatal diagnosis. Pros and cons of routine use are discussed as follows: technical aspects and design of array, yield, interpretation of copy number variants and variances of unknown significance (VOUS), quality control regimens. What does this study add? Pros and cons of routine use are discussed as follows: technical aspects and design of array, yield, interpretation of copy number variants and variances of unknown significance (VOUS), quality control regimens. © 2013 John Wiley & Sons, Ltd.
Bennett C.E.,University of Exeter |
Conway G.S.,University College London |
MacPherson J.N.,Wessex Regional Genetics Laboratory |
Jacobs P.A.,Wessex Regional Genetics Laboratory |
Murray A.,University of Exeter
Human Reproduction | Year: 2010
BACKGROUND: It is recognized that FMR1 premutation expansions are associated with premature ovarian failure (POF), but the role of smaller repeats at the boundary of premutation and normal is less clear.METHODSWe have therefore investigated the incidence of these intermediate sized FMR1 CGG repeats (35-58 repeats) in a series of 366 women ascertained because of menopause before the age of 40.RESULTSWe found no significant difference in the incidence of intermediates in cases compared with controls. Thus, we were unable to replicate previous studies showing a positive association, despite a significantly larger sample size.CONCLUSIONSWe therefore conclude that intermediate sized FMR1 CGG repeat alleles should not be considered a high-risk factor for POF based on current evidence. © 2010 The Author.