Nfa research projects

Recent news on face transplants

As a charity the NfA welcomes new medical techniques and treatments that offer hope to people with the diagnosis of Nf. We shall wait for news of the outcome of this process with great interest.

Unlike the 2 previous recipients of a face transplant, this man was not damaged by sudden trauma but suffered one of the rarer complications of Nf, causing a disfiguring tumour to grow on the face. This in itself adds a new dimension to this procedure, particularly in the healing of the facial tissues.

We wish the patient well and a swift recovery, and acknowledge the generosity of the donor family.

To read the full story, click here: http://news.bbc.co.uk/1/hi/health/6290301.stm

Manchester Group

Nf1

Also, partly through help from NfA, a research doctor, Saba Sharif, is conducting a long term follow up study of Nf1 patients who have been diagnosed with optic nerve sheath gliomas. She is looking at the incidence of second tumours, long term survival and quality of life. She has collected patients from Manchester, Guy's hospital in London and Oxford. She is also looking in collaboration with Cardiff to see if certain genetic changes make optic nerve tumours more likely

Nf2

With our work on blood and tumour samples in Nf2 patients we have now established that the prevalence of somatic mosaicism in Nf2 new mutations (affected patients without an affected parent) is 25-28%, higher than previous estimates of 15-20%. Mosaicism is when a patient with Nf2 has not inherited the gene fault from the egg or sperm, but this occurs later in development as an embryo. The risk of disease transmission from mosaic parents to offspring is very low when the constitutional Nf2 mutation cannot be identified in the parent's blood sample using standard mutation techniques such as SSCP/HA.

We have also recently collected a series of Nf2 patiemnts who have unusual chromosomal changes affecting chromosome 22 causing their Nf2.

Finally we have published our research showing that Nf2 patients have much better outcome when treated at a specialist centre.

NF Publications since 2001

Singhal S, Kerr B, Birch J, Lashford L, Evans DGR. Clinical characteristics of symptomatic sporadic and Nf1 related optic gliomata: implications for management. Archives Dis Child 2002; 87:65-70.

Baser ME, Friedman JM, Aeschilman D, Joe H, Wallace AJ, Ramsden RT, Evans DGR. Predictors of the risk of mortality in neurofibromatosis 2. Am J Hum Genet 2002; 71: 715-23.

Zhao Y, Kumar RA, Baser M, Evans DGR, Kluwe L, Mautner VF, Parry DM, Rouleau GA, Wallace A, Joe H, Friedman JM. Intrafamilial correlation of clinical manifestations in neurofibromatosis 2 (NF2). Genetic Epidemiology 2002; 23(3):245-59.

Woods R, Friedman JM, Evans DGR, Baser M, Joe H. Exploring the ‘2-Hit Hypothesis' in Nf2: Tests of 2-Hit and 3 Hit models of vestibular schwannoma development. Genetic Epidemiology 2003; 24:265-72.

Mohyuddin A, Vokurka EA, Evans GR, Ramsden RT, Jackson A. Is Clinical Growth Index A Reliable Predictor of Tumour Growth In Vestibular Schwannomas? Clin Otolaryngol 2003; 28(2):85-90.

Baser ME, Evans DGR, Gutmann DH. Neurofibromatosis 2. Current Opin Neurol 2003; 16:27-33.

Evans DGR, Scheithauer B, Komminoth P, Peltonen J. Neurofibromatosis 1, in WHO Endocrine tumors. IARC press, Lyon, in press.

Tsilchorozidou T, Menko F, Lalloo F, Kidd A, Da Silva R, Smith P, Malcolmson A, Dore J, Madan K, Brown A, Yovos JG, Tsaligopoulos M, Vogiatzis N, Wallace A, Evans DGR. Constitutional rearrangements of chromosome 22 as a cause of neurofibromatosis type 2. J Med Genet 2003; submitted

Evans DGR, Moran A, King A, Saeed S, Gurusinghe N, Ramsden R. Incidence of Vestibular Schwannoma and Neurofibromatosis 2 in the North West of England over a 10 year period: higher incidence than previously thought. Otol Neurotol 2003

Evans DGR, Baser ME, O'Reilly B, et al. Management of the patient and family with neurofibromatosis 2: a consensus conference statement. Lancet Neurology 2003 submitted

Woods R, Friedman JM, Evans DGR, Baser M, Joe H. Exploring the ‘2-Hit Hypothesis' in NF2: Tests of 2-Hit and 3 Hit models of vestibular schwannoma development. Genetic Epidemiology 2003; 24:265-72.

Mohyuddin, A; Vokurka, EA; Evans GR; Ramsden, RT, Jackson A. Is Clinical Growth Index A Reliable Predictor of Tumour Growth In Vestibular Schwannomas? Clin Otolaryngol 2003; 28(2):85-90.

Szudek J, Evans DG, Friedman JM. Patterns of associations of clinical features in neurofibromatosis 1 (NF1). Hum Genet 2003;112(3):289-97

Moyhuddin A, Baser ME, Watson C, Purcell S, Ramsden RT, Heiberg A, Wallace AJ, Evans DGR. Somatic mosaicism in neurofibromatosis 2: prevalence and risk of disease transmission to offspring. J Med Genet 2003; 40: 459-63.

Mantripragada KK, Buckley PG, Benetkiewicz M, De Bustos C, Hirvela C, Jarbo C, Bruder CE, Wensman H, Mathiesen T, Nyberg G, Papi L, Collins VP, Ichimura K, Evans G, Dumanski JP. High-resolution profiling of an 11 Mb segment of human chromosome 22 in sporadic schwannoma using array-CGH. Int J Oncol. 2003; 22(3):615-22.

Baser ME, Kuramoto L, Joe H, Friedman JM, Wallace AJ, Ramsden RT, Evans DG. Genotype-phenotype correlations for cataracts in neurofibromatosis 2. J Med Genet. 2003;40(10):758-60

Warren C, James LA, Varley JM, Ramsden RT, Evans DG. Identifying Recurrent Regions of Chromosome Loss and Gain in 76 Vestibular Schwannomas Using Comparative Genomic Hybridisation (CGH). J Med Genet 2003; 40(11):802-6.

Gutmann DH, James CD, Poyhonen M, Louis DN, Ferner R, Guha A, Hariharan S, Viskochil D, Perry A.Molecular analysis of astrocytomas presenting after age 10 in individuals with NF1. Neurology. 2003 Nov 25;61(10):1397-400.

Listernick R, Ferner RE, Piersall L, Sharif S, Gutmann DH, Charrow J. Late-onset optic pathway tumors in children with neurofibromatosis 1. Neurology. 2004;63(10):1944-6.

Ferner RE, Hughes RA, Hall SM, Upadhyaya M, Johnson MR. Neurofibromatous neuropathy in neurofibromatosis 1 (NF1). J Med Genet. 2004 Nov;41(11):837-41

Baser ME, Kuramoto L, Joe H, Friedman JM, Wallace AJ, Gillespie JE, Ramsden RT, Evans DG. Genotype-Phenotype Correlations for Nervous System Tumors in Neurofibromatosis 2: A Population-Based Study. Am J Hum Genet. 2004;75(2). [Epub ahead of print]

Tsilchorozidou T, Menko F, Lalloo F, Kidd A, Da Silva R, Smith P, Malcolmson A, Dore J, Madan K, Brown A, Yovos JG, Tsaligopoulos M, Vogiatzis N, Wallace A, Evans DGR. Constitutional rearrangements of chromosome 22 as a cause of neurofibromatosis type 2. J Med Genet 2004; 41(7):529-34

Wegner EA, Barrington SF, Kingston JE, Robinson RO, Ferner RE, Taj M, Smith MA, O'doherty MJ.The impact of PET scanning on management of paediatric oncology patients. Eur J Nucl Med Mol Imaging. 2005 Jan;32(1):23-30. Epub 2004 Jul 31.

Evans DG, Watson C, King A, Wallace A. Multiple meningiomatosis: differential involvement of NF2 in children and adults. J Med Genet 2005; 42(1):45-8

Evans DGR, Moran A, King A, Saeed S, Gurusinghe N, Ramsden R. Incidence of Vestibular Schwannoma and Neurofibromatosis 2 in the North West of England over a 10 year period: higher incidence than previously thought. Otol Neurotol 2005; in press

Evans DGR, Baser ME, O'Reilly B, et al. Management of the patient and family with Neurofibromatosis 2: a consensus conference statement. Brit J Neurosurg 2005: in press

Baser ME, Kuramoto L, Woods R, Joe H, Friedman JM,Wallace AJ, Ramsden RT, Olschwang S, Bijlsma E, Kalamarides M, Papi L, Kato L, Evans DG. The location of constitutional neurofibromatosis 2 (NF2) splice-site mutations is associated with the severity of NF2. J Med Genet 2005; in press.

King A, Biggs N, Ramsden RT, Wallace A, Gillespie J, Evans DGR. Spinal tumors in neurofibromatosis type 2: is emerging knowledge of genotype predictive of natural history? J Neurosurg 2005; in press.

Evans DGR, Maher ER, Baser ME. Age-related shift in the mutation spectra of germline and somatic NF2 mutations: hypothetical role of DNA repair mechanisms. J Med Genet 2005; in press

Baser ME, Rai H, Wallace AJ, Evans DGR. Neurofibromatosis 2 and malignant mesothelioma in an elderly man. Familial Cancer 2005: in press.

Research into Neurofibromatosis type 1 –
Dr Meena Upadhyay, University Hospital of Wales, Cardiff

Our past and current projects involve the following research areas:

• The development of high-throughput and sensitive mutation detection techniques for the rapid analysis of NF1 gene.
• The determination and comparison of the germline and somatic mutational spectra of the NF1 gene.
• An elucidation of how NF1 gene mutations contribute to the formation of NF1-associated tumours, as well as assessing the potential role of the NF1 gene in tumorigenesis.
• A study of the nature of the molecular mechanisms underlying the transformation of NF1-related benign tumours to malignancy.
• A study of the possible role of allelic heterogeneity at the NF1 locus in determining the associated clinical phenotype.
• The analysis of the potential role of the modifying genetic loci in the variable clinical variable expression of NF1 seen in patients.
• An investigation of the association between NF1 gene lesions and mismatch repair gene defects.
• The search for mutations within the NF1 gene promoter region and the use of these mutations as tools to perform structure/function studies of the gene.
• Ascertainment of the possible role of methylation of the NF1 gene promoter in gene inactivation and tumorigenesis.
• The utilisation of mutation data to help identify novel functional domains in neurofibromin, the NF1 gene product.
• A study of the molecular mechanisms underlying the rare segmental forms of NF1. To test the hypothesis that this disease entity is due to somatic mosaicism.
• The use of cDNA microarrays to study the downstream effects of NF1 gene lesions on cellular gene expression.

Funding Agencies
We are grateful to NF Association, The Action Research, Smith Charities, the Hayley Trust, the National Lottery Board and the International Association of Cancer Research for their financial support.
A major area of our research work has involved the analysis of both large and small NF1 gene mutations in a large panel of affected individuals for NF1 using different techniques: viz. single strand conformation polymorphism (SSCP), high-throughput heteroduplex analysis, dideoxyfingerprinting, RNA-PCR, protein truncation test (PTT), denaturing high performance liquid chromatography (dHPLC). We have also analysed mutations in several atypical NF1 families. Areas of related research include the development of fast, efficient and sensitive mutation detection techniques for direct application to clinical diagnostic practice; the in vitro expression of NF1 mutants using site-directed mutagenesis and the study of their effects on the intrinsic GAP activity of the mutant NF1 protein, more recently a comparative study of germline and somatic mutations in the NF1 gene in tumorigenesis and the molecular basis of NF1 tumorigenesis.
Our NF1 research group over the last 16 years, has made significant contributions towards the mapping and linkage analysis of the NF1 gene, detailed mutation analysis of the NF1 gene and the definition of the potential genotype/phenotype relationships of the disease
Ever since the initial establishment of the NF1 Linkage Consortium in 1987, we have been a major contributor to the cloning and mutational analysis of the NF1 gene. Dr Upadhyaya is a founding member of the:

1. NF1 Mutational Analysis Consortium Steering Committee.
2. International Consortium on NF1 and NF2 gene cloning and function co-ordinated by The National Neurofibromatosis Foundation Inc.

Our research group have published one of the largest data sets of NF1 mutations that has We have played a leading role in the development of sensitive mutation detection techniques for NF1 that are applicable to diagnostic analysis.

Dr Upadhyaya has successfully supervised 5 PhD students working on the molecular genetics of NF1 and is currently supervising another two.

Dr Meena Upadhyaya is a Senior Lecturer at the University of Wales College of Medicine and a Consultant Molecular Geneticist at the University Hospital of Wales, Cardiff, UK. She obtained her PhD in reproductive physiology from the University of Wales College of Medicine and subsequently trained in molecular genetics at the Institute of Medical Genetics, UWCM, Cardiff. She was awarded a Fellowship of the Royal College of Pathologists (FRCPath) in 2000.

'Molecular Genetic Analysis of Neurofibromatosis Type 1' Banbury Center, Cold Spring Harbor, New York, USA, October, 1990

'Analysis of mutations at the NF1 locus' 8th International Congress of Human Genetics. Washington DC, USA, 1991

Mutation Analysis in NF1. International Neurofibromatosis Symposium. Vienna, June, 1992'

Molecular analysis of NF1' at European NF1 Association, 1993, Sienna, Italy

‘Mutation analysis in DNA, RNA and protein of NF1 gene' FASEB, Santa Cruz, California, USA, 1994

Large deletions in NF1 gene and dysmorphism. American Society of Human Genetics, Minneapolis, USA, Oct, 1995

‘Mutational and functional analysis of NF1 gene' FACEB , Snowmas Village, Colorado , USA,1996

Molecular genetics of NF1', University of California, LA, USA, 1996

Molecular genetics of NF1', Berlin, Germany, February, 1998

Molecular genetics of NF1' at Convegno sulle Neurofibromatosi e sulla Sclerosi Tuberosa, 7 June, 1998 Universita degli studi Catania, Sicily, Italy.

Mutation analysis in NF1 promoter at eighth European Neurofibromatosis Meeting, Ulm, Germany 24 September, 1999

Application of DHPLC to NF1 mutation analysis Ninth European NF Meeting, Venice, May, 2001

Molecular Genetics of NF1 tumorigenesis at the neurofibromatoses at IRCCS Neuromed Centro Ricerche, Pozzilli, Rome, Italy, May, 2003

Molecular dissection of NF1 tumorigenesis: comparison of germline and somatic NF1 gene mutations at The 10th European Neurofibromatosis Meeting, Turku, Finland 23-27July, 2003

NF1 tumorigenesis at International Workshop on the diagnosis and management of central nervous system and peripheral nerve tumours in NF1 patients. Padua, italy, 18th-20th Nov, 2003.

Dr Upadhyaya has given oral presentations at:
All the Conferences organised by the International Consortium on NF1 and NF2 on gene cloning and function (1-2 meetings per year in USA) from 1987 to 2000
Dr Upadhyaya has been on NF1 Mutation Analysis Consortium Steering Committee since 1990.
An active member of the International Consortium on NF1, NF2 gene cloning and function

PUBLICATIONS & BOOKS
Upadhyaya M, Cooper DN (1998) Neurofibromatosis type 1: From Genotype To Phenotype Eds M Upadhyaya and DN Cooper, BIOS Publishers, Oxford Chapters in Books

CHAPTERS IN BOOKS:   « top »
Huson S, Upadhyaya M (1994) Neurofibromatosis 1: Clinical management and genetic counselling. Chapter 15 In: the Neurofibromatosis: A pathogenetic and clinical overview Eds. by Huson & Hughes, Chapman & Hall Medical 355-381

Upadhyaya M, Cooper DN (1998) The mutational spectrum in neurofibromatosis type 1 and its underlying mechanisms . In NF1: From Genotype To Phenotype Eds M Upadhyaya and DN Cooper, BIOS Publishers, Oxford

Maynard J, Upadhyaya M (2000) High-throughput screening for the detection of unknown mutations: improved productivity using heteroduplex analysis. In:Polymorphism detection and analysis Eds John D Burczak and Elaine Mardis, Eaton Publishing, Canada

Upadhyaya M, Thompson P, Han S, Cooper DN (2003) Neurofibromatosis type 1 (NF1)- a common familial cancer syndrome. Chapter 15, In Molecular Diagnosis of Genetic Diseases. Ed Elles R, Mountford R, Second Edition, Humana Press Inc. pp 285-310

Upadhyaya M, Cooper DN (2003) Genetics of Neurofibromatosis Type 1. In The Encyclopedic Reference of Genomics and Proteomics in Molecular Medicine. Ed JT Epplen, Springer-Verlag.( In Press).

RESEARCH PAPERS & REVIEWS
Upadhyaya M, Sarfarazi M, Huson S, Harper PS (1987) Further exclusion data for von Recklinghausen neurofibromatosis gene: a genetic linkage study of 19 polymorphic markers J Med Genet 24: 534 - 536

Seizinger BR, Rouleau GA, Ozelius Z, Lane AH, Faryniarz AG, Chao MV, Huson S, Korf BR, Parry DM, Pericak-Vance MA, Collins FS, Hobbs WJ, Falcone JA, Roy JC, St.George-Hyslop PH, Tanzi RE, Bothwell MA, Upadhyaya M, Harper P Goldstein AE, Hoover DL, Bader JL, Spence MA, Mulvhill JJ, Aylsworth AS, Vance JM, Rossenwasswer GOD, Gaskell PC, Roses AD, Martuza RL, Breakefield XO and JF Gusella. (1987) Genetic linkage of von Recklinghausen neurofibromatosis to the nerve growth factor receptor gene. Cell 49: 589-594

Upadhyaya M, Sarfarazi M, Huson S,Stephens K, Broadhead W, Harper PS (1987) Chromosome 17 markers and von Recklinghausen neurofibromatosis - a genetic linkage study in British population. Genomics 1: 358 - 360

Upadhyaya M, Sarfarazi M, Huson SM, Broadhead W, Fryer A, Harper PS (1989) Close flanking markers for neurofibromatosis type 1 (NF1). Am J Hum Genet 44: 41- 47

Jadayel D, Fain P Upadhyaya M, Ponder MA, Huson SM, Carey J, Fryer A, Mathew CGP, Barker DF, Ponder BAJ (1990) Paternal origin of new mutations in von Recklinghausen neurofibromatosis (NF1). Nature 343: 558-559

Brooke JD, Upadhyaya M, Broadhead W, Rundle S, Walsh KV, Harley HG, Shaw DJ (1990) A Hind III polymorphism identified by DNA clone which maps to chromosome 17 (D17S245). Nucleic Acids Res 18: 1043

Upadhyaya M, Cherryson A, Broadhead W, Fryer A, Huson S, Wallace MR, Andersen LB, Marchuk DA, Viskochil D, Black D, Harper PS, O'Connell P, Collins FS (1990) A 90kb DNA deletionassociated with neurofibromatosis. J Med Genet 27: 738-741

Allanson JE, Upadhyaya M, Watson GH, Partington M, Lahey et al (1991) Watson syndrome: Is it a sub-type of neurofibromatosis? J Med Genet 28: 752-756

Upadhyaya M, Shen M, Cherryson A, Farnham J, Maynard J, Huson SM, Harper PS (1992) Analysis of mutations in neurofibromatosis type 1. Hum Mol Genet 1: 735- 740

Shen M, Upadhyaya M (1993) A novel mutation in exon 28 of NF1 gene. Hum Genet 92: 410-412

Shen MH, Harper PS, Upadhyaya M (1993) Neurofibromatosis type 1 (NF1): The search for mutations by PCR heteroduplex analysis on Hydrolink gels. Hum Mol Genet 2: 1861-1864

Upadhyaya M, Shaw DJ, Harper PS (1994) Molecular basis of neurofibromatosis type1 (NF1): Mutation analysis and polymorphisms in the NF1 gene. Hum Mutation4: 83-101

Shen M, Harper PS, Upadhyaya M (1995) Amplification of the coding sequence of the NF1 gene from peripheral blood lymphocytes RNA. PCR Meth Appl 4: 311-313

Upadhyaya M, Maynard J, Osborn M, Huson S, Ponder M, Ponder B, Harper PS (1995) Characterisation of mutations in the NF1 gene. J Med Genet 32: 706-710

Shen MH, Harper PS, Upadhyaya M (1995) Molecular genetics of neurofibromatosis type 1 (NF1) region. J Med Genet 33: 2-17

Mann S, McDowell HP,Upadh yaya M, Fryer A (1995) Vaginal rhabdomyosarcoma in a patient with Noonan syndrome. J Med Genet 32: 743-745

Shen MH, Upadhyaya M (1995) Two single base polymorphisms in introns 41 and 16 of the NF1 gene. Am J Med Genet 60: 147-149

Upadhyaya M, Roberts S, Maynard J, Sorour E, Thompson P, Vaughan M, WIlkie A,Hughes H (1995) A large cytogenetic deletion in a patient with sporadic neurofibromatosis type 1 (NF1), associated with dysmorphism and developmental delay J Med Gen 33: 148-152

Upadhyaya M, Osborn M, Maynard J, Harper PS (1996) Characterisation of 6 mutations in exon 37 of NF1 gene. Am J Med Genet 67: 421-423

Upadhyaya M, Maynard J, Osborn M, Harper PS (1997) Six novel mutations in the NF1 gene. Hum Mutation,10 : 248-250

Upadhyaya M, Osborn M, Maynard J, Kim MR, Tamanoi F,Cooper DN (1997)

Mutational and functional analysis of NF1. Hum Genet 99: 88-92

Maynard J, Krawczak M, Upadhyaya M (1997) Characterisation and significance of nine novel mutations in exon 16 of neurofibromatosis type 1 (NF1) gene. Hum. Genet 99: 674-676

Upadhyaya M, Ruggieri M, Maynard J, Osborn M, Hartog C, Mudd S, Penttinen M, Cordeiro I, Ponder M, Ponder BAJ, Krawczak M, Cooper DN (1998) Gross deletions of the neurofibromatosis type 1( NF1) gene are predominantly of maternal origin and commonly associated with a learning disability, dysmorphic features and developmental delay. Hum. Genet. 102: 591-597

Maynard JH and Upadhyaya M (1998) High throughput screening for the detection of unknown mutations: Improved productivity using heteroduplex analysis. Biotechniques 25: 648-651

O'Donovan. M, Oefner PJ, Roberts SC, Jehannine A, Hoogendoorn B, Guy, C,Speight G, Upadhyaya M, Sommer SS, McGuffin P (1998) Blind analysis of denaturing high- performance liquid chromatography as a tool for mutation detection. Genomics 52: 44-49

Cowley GS, Murthy AE, Parry DM, Schneider G, Korf B, Upadhyaya M, Harper PS, MacCollin, Bernards A, Gusella JF (1998) Genetic variation in the 3' untranslated region of the neurofibromatosis gene: application to unequal allelic expression. Somat. Cell Mol Genet 24: 107-119

Faravelli F, Upadhyaya M, Osborn M, Huson S, Hayward R, Winter R (1999) Unusual recurrence of brain tumours in a family with NF1. J Med. Genet 36:893-896

Osborn M, Upadhyaya M (1999) Evaluation of protein truncation test for mutation detection in the NF1 gene: mutational analysis of 15 known and 40 unknown NF1

Osborn M, Cooper DN, Upadhyaya M (2000) Molecular analysis of the 5'- flanking region of the neurofibromatosis type 1( NF1) gene: identification of five sequence variants in NF1 patients. Clin Genet 57:221-224

King A, Upadhyaya M, Penney C, Doshi R (2000) A case of Miller_Dieker Syndrome in a family with neurofibromatosis type 1. Acta Neuropatholog 99:425-427

Horan Martin, Cooper DN, Upadhyaya M (2000) Site-specific methylation of the neurofibromatosis type 1 gene promoter bis rarely involved in NF1 gene inactivation in NF1-specific tumours. Human Genetics 107:33-39

Ruggieri M, D'Arrigo G, Abbate M, Distefano A, Upadhyaya M (2000) Multiple coronary artery aneurysms in a child with neurofibromatosis type 1. Eur J Pediatr 159:477-80

John A, Ruggieri M, Ferner R, UpadhyayaM (2000) A search for evidence of somatic mutation of the NF1 gene , J Med Genet 37: 44-49

Lopez-Correa C, Dorscher M, Brems H, Lazaro C, Clementi M, Upadhyaya M, Dooijes D, Moog U, Kehrer-Sawatzki H, Rutkowski JL, Fryns JP, Marynen P, Stephens K, Legius E (2001 Recombination hotspot in NF1 microdeletion patients. Hum Mol Genet 10: 1387-1392

Han S, Cooper DN, Upadhyaya M (2001) Evaluation of denaturing high performance liquid chromatography (DHPLC) for mutational analysis of the neurofibromatosis type 1 (NF1) gene. Hum Genet , 109: 487-497

Upadhyaya M, Cooper DN (2002) Detection of NF1 mutations utilising the Protein Truncation Test (PTT). In Neurogenetics: Methods and Protocols. Eds Nicholas T Potter Humana Press

Oktenli C, Saglum M, Demirbas S, Thompson P, Upadhyaya M, Ulucan H, Koz C, Durukan A, Bozkurt A, Kocar IH, Gul D (2002) A large deletion (1.5 Mb) encompassing the neurofibromatosis type 1 (NF1) gene in a patient with sporadic NF1 associated with dysmorphism, mental retardation, unusual ocular and skeletal features. Clin Morphol (In Press)

Ferner RE, Gutmann DH, Consortium (2002) International Consensus Statement on malignant peripheral nerve sheath tumours in neurofibromatosis 1. Cancer Res 62: 1573-1577

Wang Q, Montmain G, Ruano E, Upadhyaya M, Dudley S, Liskay MR, Thibodeau SN, Puisieux A (2003) The neurofibromatosis type 1 gene as a mutational target in mismatch repair-deficient cells. Hum Genet 112: 117-123

Upadhyaya M, Majounie E, Thompson P, Han S, Consoli C, Krawczak M, Cordeiro I, Cooper DN (2003) Three pathological lesions in the NF1 gene originating de novo in a family with neurofibromatosis type 1. Hum Genet 112:12-17

Upadhyaya M, Han S, Consoli C, Majounie E, Horam M, Thomas N, Potts C, Griffiths S, Ruggieri M, von Deimling,A, Cooper DN (2003) Characterisation of somatic mutational spectrum of neurofibromatosis type 1 (NF1) gene in neurofibromatosis patients with benign and malignant tumours. Hum Mut (In Press)

Castle B, Baser ME, Huson SM, Cooper DN, Upadhyaya M. Evaluation of genotype-phenotype correlations in neurofibromatosis type 1. J Med Genet. 2003 Oct;40(10):e109.

Oktenli C, Saglam M, Demirbas S, Thompson P, Upadhyaya M, Consoli C, Ulucan H, Koz C, Durukan AH, Bozkurt A, Koc B, Kocar IH, Gul D A large deletion (1.5 Mb) encompassing the neurofibromatosis type 1 (NF1) gene in a patient with sporadic NF1 associated with dysmorphism, mental retardation, and unusual ocular and skeletal features. Clin Dysmorphol. 2003 Jul;12(3):199-201.

Wang Q, Montmain G, Ruano E, Upadhyaya M, Dudley S, Liskay RM, Thibodeau SN, Puisieux A.Neurofibromatosis type 1 gene as a mutational target in a mismatch repair-deficient cell type. Hum Genet. 2003 Feb;112(2):117-23. Epub 2002 Nov 21

Upadhyaya M, Osborn M, Cooper DN.Detection of NF1 mutations utilizing the protein truncation test (PTT). Methods Mol Biol. 2003;217:315-27.

Upadhyaya M, Majounie E, Thompson P, Han S, Consoli C, Krawczak M, Cordeiro I, Cooper DN.Three different pathological lesions in the NF1 gene originating de novo in a family with neurofibromatosis type 1. Hum Genet. 2003 Jan;112(1):12-7.

Ferner RE, Hughes RA, Hall SM, Upadhyaya M, Johnson MR Neurofibromatous neuropathy in neurofibromatosis 1 (NF1). J Med Genet. 2004 Nov;41(11):837-41.

Horan MP, Osborn M, Cooper DN, Upadhyaya M Functional analysis of polymorphic variation within the promoter and 5' untranslated region of the neurofibromatosis type 1 (NF1) gene. Am J Med Genet. 2004 Dec 15;131A(3):227-31

Oktenli C, Gul D, Deveci MS, Saglam M, Upadhyaya M, Thompson P, Consoli C, Kocar IH, Pilarski R, Zhou XP, Eng C. Unusual features in a patient with neurofibromatosis type 1: multiple subcutaneous lipomas, a juvenile polyp in ascending colon, congenital intrahepatic portosystemic venous shunt, and horseshoe kidney. Am J Med Genet. 2004 Jun 15;127A(3):298-301.

Venturin M, Gervasini C, Orzan F, Bentivegna A, Corrado L, Colapietro P, Friso A, Tenconi R, Upadhyaya M, Larizza L, Riva P.Evidence for non-homologous end joining and non-allelic homologous recombination in atypical NF1 microdeletions. Hum Genet. 2004 Jun;115(1):69-80. Epub 2004 Apr 21.

Upadhyaya M, Thompson P, Han S, Cooper DN Neurofibromatosis type 1: a common familial cancer syndrome. Methods Mol Med. 2004;92:285-310.

Venturin M, Guarnieri P, Natacci F, Stabile M, Tenconi R, Clementi M, Hernandez C, Thompson P, Upadhyaya M, Larizza L, Riva P.Mental retardation and cardiovascular malformations in NF1 microdeleted patients point to candidate genes in 17q11.2. J Med Genet. 2004 Jan;41(1):35-41.

Upadhyaya M, Han S, Consoli C, Majounie E, Horan M, Thomas NS, Potts C, Griffiths S, Ruggieri M, von Deimling A, Cooper DN.Characterization of the somatic mutational spectrum of the neurofibromatosis type 1 (NF1) gene in neurofibromatosis patients with benign and malignant tumors. Hum Mutat. 2004 Feb;23(2):134-46.