Claire Turner
University of Southampton
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Featured researches published by Claire Turner.
European Journal of Human Genetics | 2010
Claire Turner; Deborah M. Mackay; Jonathan L. A. Callaway; Louise E Docherty; Rebecca L Poole; Hilary Bullman; Margaret Lever; Bruce Castle; Emma Kivuva; Peter D. Turnpenny; Sarju G Mehta; Sahar Mansour; Emma Wakeling; Verghese Mathew; Jackie Madden; Justin H. Davies; I. Karen Temple
This study was an investigation of 79 patients referred to the Wessex Regional Genetics Laboratory with suspected Russell–Silver Syndrome or unexplained short stature/intra uterine growth restriction, warranting genetic investigation. Methylation status was analysed at target sequences within eleven imprinted loci (PLAGL1, IGF2R, PEG10, MEST1, GRB10, KCNQ1OT1, H19, IGF2P0, DLK1, PEG3, NESPAS). Thirty seven percent (37%) (29 of 79) of samples were shown to have a methylation abnormality. The commonest finding was a loss of methylation at H19 (23 of 29), as previously reported in Russell–Silver Syndrome. In addition, four of these patients had methylation anomalies at other loci, of whom two showed hypomethylation of multiple imprinted loci, and two showed a complete gain of methylation at IGF2R. This latter finding was also present in five other patients who did not have demonstrable changes at H19. In total, 7 of 79 patients showed a gain of methylation at IGF2R and this was significantly different from a normal control population of 267 individuals (P=0.002). This study in patients with growth restriction shows the importance of widening the epigenetic investigation to include multiple imprinted loci and highlights potential involvement of the IGF2R locus.
Nature Genetics | 2012
Magdalena Harakalova; Jeske van Harssel; Paulien A. Terhal; Stef van Lieshout; Karen Duran; Ivo Renkens; David J. Amor; Louise C. Wilson; Edwin P. Kirk; Claire Turner; Debbie Shears; Sixto García-Miñaúr; Melissa Lees; Alison Ross; Hanka Venselaar; Gert Vriend; Hiroki Takanari; Martin B. Rook; Marcel A.G. van der Heyden; Folkert W. Asselbergs; Hans M Breur; Marielle Swinkels; Ingrid Scurr; Sarah F. Smithson; Nine V.A.M. Knoers; Jasper J. van der Smagt; Isaac J. Nijman; Wigard P. Kloosterman; Mieke M. van Haelst; Gijs van Haaften
Cantú syndrome is characterized by congenital hypertrichosis, distinctive facial features, osteochondrodysplasia and cardiac defects. By using family-based exome sequencing, we identified a de novo mutation in ABCC9. Subsequently, we discovered novel dominant missense mutations in ABCC9 in 14 of the 16 individuals with Cantú syndrome examined. The ABCC9 protein is part of an ATP-dependent potassium (KATP) channel that couples the metabolic state of a cell with its electrical activity. All mutations altered amino acids in or close to the transmembrane domains of ABCC9. Using electrophysiological measurements, we show that mutations in ABCC9 reduce the ATP-mediated potassium channel inhibition, resulting in channel opening. Moreover, similarities between the phenotype of individuals with Cantú syndrome and side effects from the KATP channel agonist minoxidil indicate that the mutations in ABCC9 result in channel opening. Given the availability of ABCC9 antagonists, our findings may have direct implications for the treatment of individuals with Cantú syndrome.
Journal of Medical Genetics | 2014
Hana Lango Allen; Richard Caswell; Weijia Xie; Xiao Xu; Christopher Wragg; Peter D. Turnpenny; Claire Turner; Michael N. Weedon; Sian Ellard
Objective Split-hand/foot malformation type 1 is an autosomal dominant condition with reduced penetrance and variable expression. We report three individuals from two families with split-hand/split-foot malformation (SHFM) in whom next generation sequencing was performed to investigate the cause of their phenotype. Methods and results The first proband has a de novo balanced translocation t(2;7)(p25.1;q22) identified by karyotyping. Whole genome sequencing showed that the chromosome 7 breakpoint is situated within the SHFM1 locus on chromosome 7q21.3. This separates the DYNC1I1 exons recently identified as limb enhancers in mouse studies from their target genes, DLX5 and DLX6. In the second family, X-linked recessive inheritance was suspected and exome sequencing was performed to search for a mutation in the affected proband and his uncle. No coding mutation was found within the SHFM2 locus at Xq26 or elsewhere in the exome, but a 106 kb deletion within the SHFM1 locus was detected through copy number analysis. Genome sequencing of the deletion breakpoints showed that the DLX5 and DLX6 genes are disomic but the putative DYNC1I1 exon 15 and 17 enhancers are deleted. Conclusions Exome sequencing identified a 106 kb deletion that narrows the SHFM1 critical region from 0.9 to 0.1 Mb and confirms a key role of DYNC1I1 exonic enhancers in normal limb formation in humans.
Genetics in Medicine | 2016
Surabhi Mulchandani; Elizabeth J. Bhoj; Minjie Luo; Nina Powell-Hamilton; Kim Jenny; Karen W. Gripp; Miriam Elbracht; Thomas Eggermann; Claire Turner; I. Karen Temple; Deborah J.G. Mackay; Holly Dubbs; David A. Stevenson; Leah Slattery; Elaine H. Zackai; Nancy B. Spinner; Ian D. Krantz; Laura K. Conlin
Purpose:Maternal uniparental disomy of chromosome 20 (UPD(20)mat) has been reported in only four patients, three of whom also had mosaicism for complete or partial trisomy of chromosome 20. We sought to evaluate the clinical significance of isolated UPD(20)mat in eight individuals.Methods:We evaluated phenotypic and genomic findings of a series of eight new patients with UPD(20)mat.Results:All eight individuals with UPD(20)mat had intrauterine growth restriction, short stature, and prominent feeding difficulties with failure to thrive. As a common feature, they often required gastric tube feeds. Genomic data in most patients are indicative of UPD as a result of trisomy rescue after meiosis II nondisjunction.Conclusion:We describe the first natural history of the disorder and the results of therapeutic interventions, including the frequent requirement of direct gastric feedings only during the first few years of life, and propose that growth hormone supplementation is probably safe and effective for this condition. We suggest that UPD(20)mat can be regarded as a new imprinting disorder and its identification requires specialized molecular testing, which should be performed in patients with early-onset idiopathic isolated growth failure.Genet Med 18 4, 309–315.
Kidney International | 2009
Rodney D. Gilbert; Claire Turner; Jane Gibson; Paul Bass; Mushfequr R. Haq; Esta Cross; David J. Bunyan; Andrew Collins; William Tapper; Juliet Needell; Beverley Dell; N. E. Morton; I. Karen Temple; David O. Robinson
Diffuse mesangial sclerosis occurs as an isolated abnormality or as a part of a syndrome. Recently, mutations in phospholipase C epsilon 1 (PLCE1) were found to cause a nonsyndromic, autosomal recessive form of this disease. Here we describe three children from one consanguineous kindred of Pakistani origin with diffuse mesangial sclerosis who presented with congenital or infantile nephrotic syndrome. Homozygous mutations in PLCE1 (also known as KIAA1516, PLCE, or NPHS3) were identified following genome-wide mapping of single-nucleotide polymorphisms. All affected children were homozygous for a four-basepair deletion in exon 3, which created a premature translational stop codon. Analysis of the asymptomatic father of two of the children revealed that he was also homozygous for the same mutation. We conclude this nonpenetrance may be due to compensatory mutations at a second locus and that mutation within PLCE1 is not always sufficient to cause diffuse mesangial sclerosis.
American Journal of Medical Genetics Part A | 2008
Moira Blyth; Nicola Foulds; Claire Turner; David J. Bunyan
Marfan syndrome is an autosomal dominant condition, with manifestations mainly in the skeletal, ocular, and cardiovascular systems. The disorder is caused by mutations in fibrillin‐1 gene (FBN1). The majority of these are family‐specific point mutations, with a small number being predicted to cause exon‐skipping. To date, there have only been five reports of in‐frame exon deletions in FBN1, with the largest of these spanning three exons. Mosaicism is rarely recorded and has only been reported in the unaffected, or mildly affected, parents of probands. Here, we report on the clinical histories of two children with exon deletions in FBN1. Both have severe Marfan syndrome with significant signs in infancy. One patient has a deletion of exon 33, which has not previously been reported. The other has the largest reported deletion, which spans 37 exons, and also represents the first reported case of mosaicism in a patient with Marfan syndrome.
Heart | 2016
Mary Gable; Sarah Burton-Jones; Claire Turner; John Dean; Panayiotis Constantinou; Ingrid Scurr; Karen Low; Emma Wakeling; Ruth Newbury-Ecob; Maggie Williams
Pathogenic ELN gene mutations (ELN, MIM#130160) cause AD Supravalvular Aortic Stenosis (SVAS) a congenital narrowing of the ascending aorta, and Cutis Laxa (CL) characterised by inelastic, loose-hanging skin. Variable phenotype and penetrance is apparent. Pathogenic ELN variants result in loss of function and include frameshift (most common), nonsense, splice site and missense variants. The well characterised contiguous gene deletion syndrome, Williams-Beuren syndrome includes SVAS and encompasses at least 114kb on 7q11.23 including the ELN gene; however, there are only 5 case reports of CNVs within ELN (single or multiple exons). Bristol Genetics Laboratory provides a UKGTN approved service for ELN gene sequencing (33 coding exons). In three years, 52 UK and foreign patients with SVAS, CL or features such as pulmonary artery stenosis and aortic dilation have been tested. 18/52 (34%) patients were heterozygous for a likely pathogenic variant including frameshift (6), nonsense (4), splice (4), and missense (4). 12 of these cases were novel variants, 5 are supported by segregation analysis and 1 is sporadic. The remaining novel variants are classed as possibly pathogenic as they are phenotypically compatible. 12/35 patients negative on sequencing have so far been screened for CNVs by MLPA (MRC Holland) covering the Williams-Beuren syndrome region, including 10 exons of the ELN gene (1, 3, 4, 6, 9, 16, 20, 26, 27 and 33) and in addition a bespoke MLPA assay including probes for exons 28 to 30, 32 and 3’UTR. 4/12 (33%) patients have a heterozygous deletion within the ELNgene. A mother and daughter with pulmonary stenosis and an extended family history have a deletion spanning exons 30 to 33. This deletion was also identified in another patient with SVAS and arteriopathy. A deletion of the 5’ end of the gene, involving at least exon 1 (but not exon 3) was identified in an infant with SVAS and pulmonary branch stenosis, and a deletion involving the entire coding region of the ELN gene and at least the first two exons of the adjacent 3’ gene LIMK1 was detected in a neonate who died at 2 months with SVAS, pulmonary stenosis and mild hypoplasia with PDA. The deletion was detected in this patient’s father who consequentially was found to have an aortic regurgitation and in a subsequent pregnancy of this family which was lost at 31 weeks with pulmonary stenosis and significant aortic stenosis MLPA analysis has enhanced the clinical utility of this service giving an increased diagnostic yield in patients with SVAS and CL and related presentations.
Diabetes | 1999
Timothy M. Frayling; M. Walker; Mark McCarthy; Julie C. Evans; Lisa I. S. Allen; Stephen Lynn; Susan Ayres; B Millauer; Claire Turner; R C Turner; Mike Sampson; Graham A. Hitman; Sian Ellard; Andrew T. Hattersley
Journal of Medical Genetics | 2010
Emma Wakeling; S Abu Amero; Marielle Alders; Jet Bliek; E Forsythe; Shaji K. Kumar; Derek Lim; Fiona Macdonald; Deborah J.G. Mackay; Eamonn R. Maher; Gudrun E. Moore; Rebecca L Poole; Susan Price; Trine Tangeraas; Claire Turner; Mieke M. van Haelst; Cara Willoughby; I. Karen Temple; Jan Maarten Cobben
Archive | 2008
Moira Blyth; Nicola Foulds; Claire Turner; David J. Bunyan