Jane Hewitt

Contact

• workRoom D98 Medical School
  Queen's Medical Centre
  Nottingham
  NG7 2UH
  UK
• work0115 823 0364
• fax0115 823 0338
• jane.hewitt@nottingham.ac.uk

Biography

BA Oxford University 1982; PhD Cambridge University 1986; Research Associate, Washington University, St. Louis USA 1986-89; MRC Training Fellow, Department of Biochemistry and Molecular Genetics, St Mary's Hospital Medical School, London 1989-1992; Lecturer, School of Biology, The University of Manchester, 1992-1998; Senior Lecturer (1998), Reader (2003), Professor (2004), Institute of Genetics, University of Nottingham. BBSRC Research Development Fellow (2004).

Research Summary

My research investigates the genetic basis of disease, especially the inherited muscular dystrophies where we focus on two types. Mutations in at least five glycosylation enzymes results in abnormal… read more

Selected Publications

• COURT, F, HEWITT, J, KAY DAVIES, K, PATTON, B, UNCINI, A and WRABETZ, L. AND FELTRI, M.L., 2009. A Laminin-2, Dystroglycan, Utrophin Axis is Required for Compartmentalization and Elongation of Myelin Segments Journal of Neuroscience. 29, 3908-3919
• A LEIDENROTH, H S SORTE, G GILFILLAN, M EHRLICH, R LYLE and J E HEWITT, 2011. Diagnosis by sequencing: correction of misdiagnosis from FSHD2 to LGMD2A by whole exome analysis. European Journal of Human Genetics. In press,
• LEIDENROTH, A. and HEWITT, J.E., 2010. A family history of DUX4: phylogenetic analysis of DUXA, B, C and Duxbl reveals the ancestral DUX gene BMC Evolutionary Biology. 10, 34
• R, HARRISON, PG HITCHEN, M PANICO, HR MORRIS, D MEKHEIL, RJ PLEASS, A DELL, JE HEWITT and SM HASLAM, 2012. Glycoproteomic characterisation of recombinant mouse alpha-dystroglycan. Glycobiology. in press

• View all publications

Current Research

My research investigates the genetic basis of disease, especially the inherited muscular dystrophies where we focus on two types. Mutations in at least five glycosylation enzymes results in abnormal modification of the key muscle protein dystroglycan and are associated with a large number of congenital muscular dystrophies. We are studying the function of one of these glycosyltransferases (LARGE).

We are also interested in the autosomal dominant neuromuscular disorder facioscapulohumeral muscular dystrophy (FSHD), the third most common type of muscular dystrophy. The genetic mutation that causes FSHD is unique and involves a deletion within a tandem DNA repeat (D4Z4) on chromosome 4q35. FSHD is caused when an individual has fewer than 10 of these repeats; the mechanism hereby this deletion causes the disease is still unknown but may involve epigenetic mechanisms.

• R, HARRISON, PG HITCHEN, M PANICO, HR MORRIS, D MEKHEIL, RJ PLEASS, A DELL, JE HEWITT and SM HASLAM, 2012. Glycoproteomic characterisation of recombinant mouse alpha-dystroglycan. Glycobiology. in press
• A LEIDENROTH, H S SORTE, G GILFILLAN, M EHRLICH, R LYLE and J E HEWITT, 2011. Diagnosis by sequencing: correction of misdiagnosis from FSHD2 to LGMD2A by whole exome analysis. European Journal of Human Genetics. In press,
• MASNY, P S, CHAN, OYA, DE GREEF, J C, BENGTSSON, U, EHRLICH, M, TAWIL, R, LOCK, L F, HEWITT, J E, STOCKSDALE, J, MARTIN, J H, VAN DER MAAREL S M, AND WINOKUR, S., 2010. Analysis of allele-specific RNA transcription in FSHD by RNA-DNA FISH in single myonuclei European Journal of Human Genetics. 18, 448-456
• HEWITT JE, 2010. Investigating the functions of LARGE: lessons from mutant mice. Methods in Enzymology. 479, 367-386
• LEIDENROTH, A. and HEWITT, J.E., 2010. A family history of DUX4: phylogenetic analysis of DUXA, B, C and Duxbl reveals the ancestral DUX gene BMC Evolutionary Biology. 10, 34
• COURT, F, HEWITT, J, KAY DAVIES, K, PATTON, B, UNCINI, A and WRABETZ, L. AND FELTRI, M.L., 2009. A Laminin-2, Dystroglycan, Utrophin Axis is Required for Compartmentalization and Elongation of Myelin Segments Journal of Neuroscience. 29, 3908-3919
• HEWITT, J.E., 2009. Abnormal glycosylation of dystroglycan in human genetic disease Biochimica et Biophysica Acta - Molecular Basis of Disease. 1792, 853-861
• MOORE, C.J. AND HEWITT, J.E., 2009. Dystroglycan glycosylation and muscular dystrophy Glycoconjugate Journal. 26, 349-357
• IMPERIALI, M, SPORRI, R and HEWITT, J. AND OXENIUS, A., 2008. Post-translational modification of alpha-dystroglycan is not critical for lymphocytic choriomeningitis virus receptor function in vivo Journal of General Virology. 89, 2713-2722
• MOORE, C.J and GOH, H.T. AND HEWITT, J.E., 2008. Genes required for functional glycosylation of dystroglycan are conserved in zebrafish Genomics. 92, 159-167
• VAN REEUWIJK,, GREWAL,, SALIH,, BELTRÁN-VALERO DE BERNABÉ,, MCLAUGHLAN,, MICHIELSE,, HERRMANN,, HEWITT,, STEINBRECHER,, SEIDAHMED,, SHAHEED,, ABOMELHA,, BRUNNER, and VAN BOKHOVEN,, 2007. Intragenic deletion in the LARGE gene causes Walker-Warburg syndrome. Human Genetics. 121, 685-690
• CLAPP, J., MITCHELL, L.M., BOLLAND, D.J., FANTES, J., CORCORAN, A.E., SCOTTING, P.J., ARMOUR, J.A.L. and HEWITT. J.E., 2007. Evolutionary conservation of a coding function for D4Z4, the tandem DNA repeat mutated in facioscapulohumeral muscular dystrophy American Journal of Human Genetics. 81(2), 264-279
• BROWNING, C.A., GREWAL, P.K., MOORE, C.J. and HEWITT, J.E., 2005. A rapid PCR method for genotyping the Large^myd mouse, a model of glycosylation-deficient congenital muscular dystrophy Neuromuscular Disorders. 15(5), 331-335
• GREWAL, P.K., MCLAUGHLAN, J.M., MOORE, C.J., BROWNING, C.A. and HEWITT, J.E., 2005. Characterization of the LARGE family of putative glycosyltransferases associated with dystroglycanopathies Glycobiology. 15(10), 912-923
• VANGEEL,M. and HEWITT,J.E., 2004. Genomic analysis of the subtelomeric regions of human chromosomes 10q and 4q: relevance to FSHD. In: UPADHYAYA,M. and COOPER,D.N., eds., Facioscapulohumeral Muscular Dystrophy (FSHD): clinical medicine and molecular cell biology London: Bios Scientific Publishers. 107-116
• HEWITT,J.E., 2004. Evolution and structural organization of homeobox-containing repeat D4Z4. In: UPADHYAYA,M. and COOPER,D.N., eds., Facioscapulohumeral Muscular Dystrophy (FSHD): clinical medicine and molecular cell biology London: Bios Scientific Publishers. 85-95
• RIJKERS, T., DEIDDA, G., VAN KONINGSBRUGGEN, S., VAN GEEL, M., LEMMERS, R. J. L. F., VAN DEUTEKOM, J. C. T., FIGLEWICZ, D., HEWITT, J. E., PADBERG, G. W. and FRANTS, R. R., 2004. FRG2, an FSHD candidate gene, is transcriptionally upregulated in differentiating primary myoblast cultures of FSHD patients Journal of Medical Genetics. VOL 41(PART 11), 826-836
• SAMPSON, N. D. and HEWITT, J. E., 2003. SF4 and SFRS14, two related putative splicing factors on human chromosome 19p13.11 Gene. VOL 305(NUMBER 1), 91-100
• CLAPP, J., BOLLAND, D. J. and HEWITT, J. E., 2003. Genomic analysis of facioscapulohumeral muscular dystrophy Briefings in Functional Genomics and Proteomics. VOL 2(NUMB 3), 213-223
• GREWAL, P. K. and HEWITT, J. E., 2003. Glycosylation defects: a new mechanism for muscular dystrophy? Human Molecular Genetics. VOL 12(SPI/2), R259-R264
• WHEATLEY, A.P., BOLLAND, D.J., HEWITT, J.E., DEWAR, J.C. and HALL, I.P., 2002. Identification of the autoantigen SART-1 as a candidate gene for the development of atopy Human Molecular Genetics. 11(18), 2143-2146
• VAN GEEL, M., DICKSON, M.C., BECK, A.F., BOLLAND, D.J., FRANTS, R.R., VAN DER MAAREL, S.M., DE JONG, P.J. and HEWITT, J.E., 2002. Genomic analysis of human chromosome 10q and 4q telomeres suggests a common origin. Genomics. 79(2), 210-217
• BADENHOP, R. F., MOSES, M. J., SCIMONE, A., ADAMS, L. J., KWOK, J. B. J., JONES, A.-M., DAVISON, G., EVANS, M. R., KIRKBY, K. C. and HEWITT, J. E., 2002. Genetic Refinement and Physical Mapping of a 2.3 Mb Probable Disease Region Associated With a Bipolar Affective Disorder Susceptibility Locus on Chromosome 4q35 AMERICAN JOURNAL OF MEDICAL GENETICS. VOL 117(PART 1), 23-32
• FENTON, R. A., COTTINGHAM, C. A., STEWART, G. S., HOWORTH, A., HEWITT, J. A. and SMITH, C. P., 2002. Structure and characterization of the mouse UT-A gene (Slc14a2) American Journal of Physiology. VOL 282(ISSU 4), F630-F638
• GREWAL, P. K. and HEWITT, J. E., 2002. Mutation of Large, which encodes a putative glycosyltransferase, in an animal model of muscular dystrophy Biochimica et Biophysica Acta. VOL 1573(NUMBER 3), 216-224
• SUTTON-SMITH,M., MORRIS,H.R., GREWAL,P.K., HEWITT,J.E., BITTNER,R.E., GOLDIN,E., SCHIFFMANN,R. and DELL,A., 2002. MS screening strategies: investigating the glycomes of knockout and myodystrophic mice and leukodystrophic human brains. In: DRICKAMER, K. and DELL, A., eds., Glycogenomics: The Impact of Genomics and Informatics on Glycobiology London: Portland Press. 105-115
• HOLZFEIND, P.J., GREWAL, P.K., REITSAMER, H.A., KECHVAR, J., LASSMANN, H., HOEGER, H., HEWITT, J.E. and BITTNER, R.E., 2002. Skeletal, cardiac and tongue muscle pathology, defective retinal transmission, and neuronal migration defects in the Large^myd mouse defines a natural model for glycosylation-deficient muscle - eye - brain disorders Human Molecular Genetics. 11(21), 2673-2687
• BOLLAND, D. J. and HEWITT, J. E., 2001. Intron loss in the SART1 genes of Fugu rubripes and Tetraodon nigroviridis Gene. VOL 271(NUMBER 1), 43-49
• CHIDGCY, M., BRAKEBUSCH, C., GUSTAFSSON, E., CRUCHLEY, A., HAIL, C., KIRK, S., MERRITT, A., NORTH, A., TSELEPIS, C. and HEWITT, J., 2001. Mice lacking desmocollin 1 show epidermal fragility accompanied by barrier defects and abnormal differentiation Journal of Cell Biology. VOL 155(PART 5), 821-832
• GREWAL, P.K., HOLZFEIND, P.J., BITTNER, R.E. and HEWITT, J.E., 2001. Mutant glycosyltransferase and altered glycosylation of α-dystroglycan in the myodystrophy mouse Nature Genetics. 28(2), 151-154