Assistant Professor, Departments of Neurology and Molecular and Human Genetics

M.D., University of Pecs Medical School, Hungary, 1994
Ph.D., University of Szeged Medical School, Hungary, 2006

RESEARCH INTERESTS:

In collaboration with James R. Lupski, I am interested in translational research in Charcot-Marie-Tooth disease and related peripheral neuropathies. We are conducting studies of genotype-phenotype correlations in CMT associated with mutations in MPZ, EGR2, MFN2, SIMPLE and PMP22. As more and more sequence alterations are detected it is very important to be able to distinguish polymorphisms, disease associated rare variants and pathogenic mutations. Our emphasis is to study human mutations and establish pathogenicity by studying the segregation of the disease phenotype within families and to develop functional assays to study the effect of the mutations in vitro.

The role of constitutional gene-dosage alterations (copy-number variation CNV) in adult-onset neurological disorders has recently been shown. Duplication of APP causes autosomal dominant early-onset Alzheimer disease (AD) with cerebral amyloid angiopathy, duplication and triplication of SNCA causes familial Parkinson disease (PD), and LMNB1 duplication is causative for leukodystrophy resembling primary progressive multiple sclerosis, all confirmed by segregation analysis in autosomal dominant families. The frequency of these copy-number changes in sporadic cases has not yet been studied; however recombination in CMT1A duplication occurs de novo in 47-90 percent of cases. We are exploring the role of copy number variation in candidate genes in the most common adult neurodegenerative disease, Alzheimer disease. In an exploratory pilot study we are screening candidate genes/regions for CNV in 200 cases of AD by custom oligo array CGH. The candidate gene/region approach i) focuses the analysis and increases the likelihood of pattern recognition, ii) allows higher resolution of regions of interest, thus increasing sensitivity at reduced cost, and iii) is feasible with the ability to custom design/redesign oligo arrays at no additional cost. Follow-up case control studies will be designed to establish the significance of the identified CNV.

SELECTED PUBLICATIONS:

1. Verhoeven K, Claeys KG, Zuchner S, Schroder JM, Weis J, Ceuterick C, Jordanova A, Nelis E, De Vriendt E, Van Hul M, Seeman P, Mazanec R, Saifi GM, Szigeti K, Mancias P, Butler IJ, Kochanski A, Ryniewicz B, De Bleecker J, Van den Bergh P, Verellen C, Van Coster R, Goemans N, Auer-Grumbach M, Robberecht W, Milic Rasic V, Nevo Y, Tournev I, Guergueltcheva V, Roelens F, Vieregge P, Vinci P, Moreno MT, Christen HJ, Shy ME, Lupski JR, Vance JM, De Jonghe P, Timmerman V (2006). MFN2 mutation distribution and genotype/phenotype correlation in Charcot-Marie-Tooth type 2. Brain 129(Pt 8): 2093-2102.

2. Szigeti K, Nelis E, Lupski JR (2006). Molecular diagnostics of Charcot-Marie-Tooth disease and related peripheral neuropathies. Neuromolecular Med. 8: 243-254.

3. Szigeti K, Garcia CA, Lupski JR (2006). Charcot-Marie-Tooth disease and related hereditary polyneuropathies: molecular diagnostics determine aspects of medical management. Genet. Med. 8:86-92.

4. Shy ME, Scavina MT, Clark A, Krajewski KM, Li J, Kamholz J, Kolodny E, Szigeti K, Fischer RA, Saifi GM, Scherer SS, Lupski JR (2006). T118M PMP22 mutation causes partial loss of function and HNPP-like neuropathy. Ann. Neurol. 59: 358-364.

5. Saifi GM, Szigeti K, Wiszniewski W, Shy ME, Krajewski K, Hausmanowa-Petrusewicz I, Kochanski A, Reeser S, Mancias P, Butler I, Lupski JR (2005). SIMPLE mutations in Charcot-Marie-Tooth disease and the potential role of its protein product in protein degradation. Hum. Mutat. 2005 25: 372-383.

6. Szigeti K, Sule N, Adesina AM, Armstrong DL, Saifi GM, Bonilla E, Hirano M, Lupski JR (2004). Increased blood-brain barrier permeability with thymidine phosphorylase deficiency. Ann. Neurol. 56: 881-886.

7. Szigeti K, Wong LJ, Perng CL, Saifi GM, Eldin K, Adesina AM, Cass DL, Hirano M, Lupski JR, Scaglia F (2004). MNGIE with lack of skeletal muscle involvement and a novel TP splice site mutation. J. Med. Genet. 41: 125-129.

8. Stankiewicz P, Cheung SW, Shaw CJ, Saleki R, Szigeti K, Lupski JR (2003). The donor chromosome breakpoint for a jumping translocation is associated with large low-copy repeats in 21q21.3. Cytogenet. Genome Res. 101: 118-123.

9. Szigeti K, Saifi GM, Armstrong D, Belmont JW, Miller G, Lupski JR (2003). Disturbance of muscle fiber differentiation in congenital hypomyelinating neuropathy caused by a novel myelin protein zero mutation. Ann. Neurol. 54: 398-402.

For more publications, see listing on Pub Med.

CONTACT INFORMATION:

Kinga Szigeti, M.D. Ph.D.
Assistant Professor
Department of Neurology - Neurosensory Center
6501 Fannin, NB 302
Houston, TX 77030-3411

Phone: 713-798-8183
E-mail:

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