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Dixit A.,Nottingham City Hospital | McKee S.,Northern Ireland Regional Genetics Service | Mansour S.,St Georges, University of London | Mehta S.G.,East Anglian Medical Genetics Service | And 7 more authors.
Clinical Genetics | Year: 2013

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. © 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd. Source

Raymond F.L.,University of Cambridge | Whittaker J.,East Anglian Medical Genetics Service | Jenkins L.,North East Thames Regional Molecular Genetics Laboratory | Lench N.,North East Thames Regional Molecular Genetics Laboratory | Chitty L.S.,University College London
Prenatal Diagnosis | Year: 2010

Originally prenatal diagnosis was confined to the diagnosis of metabolic disorders and depended on assaying enzyme levels in amniotic fluid. With the development of recombinant DNA technology, molecular diagnosis became possible for some genetic conditions late in the 1970s. Here we briefly review the history of molecular prenatal diagnostic testing, using Duchenne muscular dystrophy as an example, and describe how over the last 30 years we have moved from offering testing to a few affected individuals using techniques, such as Southern blotting to identify deletions, to more rapid and accurate PCR-based testing which identifies the precise change in dystrophin for a greater number of families. We discuss the potential for safer, earlier prenatal genetic diagnosis using cell free fetal DNA in maternal blood before concluding by speculating on how more recent techniques, such as next generation sequencing, might further impact on the potential for molecular prenatal testing. Progress is not without its challenges, and as cytogenetics and molecular genetics begin to unite into one, we foresee the main challenge will not be in identifying the genetic change, but rather in interpreting its significance, particularly in the prenatal setting where we frequently have no phenotype on which to base interpretation. Copyright © 2010 John Wiley & Sons, Ltd. Source

Hughes L.,East Anglian Medical Genetics Service | Phelps C.,University of Swansea
Journal of Genetic Counseling | Year: 2010

There is increasing evidence to suggest that the ongoing information and support needs of BRCA gene mutation carriers are not being met. This qualitative study investigated preferences for an on-going support network for mutation carriers in Wales, UK. Seventeen female BRCA1/2 mutation carriers participated in focus groups which explored their current and on-going information and psychological support needs. The interviews were transcribed and thematically analysed. The results reflected a diversity of experiences and support needs. The majority of participants felt they and their families would benefit from an on-going 'support network' which should incorporate information-provision alongside elements of a traditional support group alongside, internet-based support such as web-based chat forums, matching schemes and professionally led workshops. Some degree of professional input into any such initiative was believed to be important. This study has informed the development of an appropriate support network based on a hub and spoke model to help carriers and their families adapt to living and coping with their genetic risk. © National Society of Genetic Counselors, Inc. 2010. Source

McMillin M.J.,University of Washington | Below J.E.,University of Washington | Shively K.M.,University of Washington | Beck A.E.,University of Washington | And 16 more authors.
American Journal of Human Genetics | Year: 2013

Distal arthrogryposis (DA) syndromes are the most common of the heritable congenital-contracture disorders, and ∼50% of cases are caused by mutations in genes that encode contractile proteins of skeletal myofibers. DA type 5D (DA5D) is a rare, autosomal-recessive DA previously defined by us and is characterized by congenital contractures of the hands and feet, along with distinctive facial features, including ptosis. We used linkage analysis and whole-genome sequencing of a multiplex consanguineous family to identify in endothelin-converting enzyme-like 1 (ECEL1) mutations that result in DA5D. Evaluation of a total of seven families affected by DA5D revealed in five families ECEL1 mutations that explain ∼70% of cases overall. ECEL1 encodes a neuronal endopeptidase and is expressed in the brain and peripheral nerves. Mice deficient in Ecel1 exhibit perturbed terminal branching of motor neurons to the endplate of skeletal muscles, resulting in poor formation of the neuromuscular junction. Our results distinguish a second developmental pathway that causes congenital-contracture syndromes. © 2013 The American Society of Human Genetics. Source

Strehle E.-M.,Northumbria University | Gruszfeld D.,Childrens Memorial Health Institute | Schenk D.,North Tyneside General Hospital | Mehta S.G.,East Anglian Medical Genetics Service | And 2 more authors.
Gene | Year: 2012

Deletions of the long arm of chromosome 4 detectable by cytogenetic analysis (standard karyotyping), fluorescent in situ hybridisation (FISH), multiplex ligation-dependent probe amplification (MLPA) or comparative genomic hybridisation (CGH) cause 4q- syndrome. Here we describe 3 cases of 4q- syndrome which demonstrate the variations in clinical presentation, diagnosis and prognosis observed in this condition. Patient 1 was a female foetus diagnosed with del(4)(q33) following chorionic villus sampling (CVS) at 14. weeks, and the pregnancy was terminated at 18. weeks. Patient 2 was a 5-month-old boy with del(4)(q31.3) and complex congenital heart disease. He also had a duplication of chromosome 6p and died of cardiac failure. Patient 3 is a 2-year-old girl with mild dysmorphic features and an interstitial deletion del(4)(q22.1q23). She has no major malformations and only slight developmental delay. © 2012 Elsevier B.V. Source

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