Kevin M. Flanigan, M.D.
Nationwide Children's Hospital
Center for Gene Therapy, WA4023
700 Children's Drive
Columbus, OH 43209
Fax: (614) 722-3273
Education & Training:
University of Illinois, Urbana/Champaign, 1986 B.M. in Trumpet Performance
Rush Medical College, Chicago, Illinois, 1990 M.D.
University of Michigan, Ann Arbor 1990-91 Internship (Internal Medicine)
The Johns Hopkins Hospital, Baltimore 1991-94 Residency (Neurology)
The Johns Hopkins Hospital, Baltimore 1994-95 Postdoctoral Fellow (Neuromuscular Disease)
University of Utah, Salt Lake City 1995-97 Postdoctoral Fellow (Neurogentics/Molecular Biology)
In the laboratory we study mechanisms of pathogenesis in the muscular dystrophies, and in the clinic setting, we seek to bring novel therapies to patient-based clinical trials. The most common form of muscular dystrophy are the dystrophinopathies, which include the more severe Duchenne Muscular Dystrophy (DMD) and the milder Becker Muscular Dystrophy (BMD). Both DMD and BMD are caused by mutations in the DMD gene, encoding the dystrophin protein. The major determinant of severity is whether the mutation results in an mRNA that maintains an open reading frame that allows translation of a functional amino- and carboxy terminus, with little impact due to the size of the central rod domain deletion. In our lab, we study genotype/phenotype correlations with a specific eye toward exceptions to this reading frame rule, and seek to determine what these mutations tell us about dystrophin function and DMD disease pathogenesis. As one example, we have recently defined the first founder disease allele in the DMD gene; this mutation, along with other nonsense mutations in the 5’ end of the gene, is associated with very mild BMD, and we have recently defined the alternate translational initiation sites within DMD exon 6 responsible for phenotypic rescue. Other mutations identified from patients have led to ongoing projects that seek to define the function of the dystrophin ZZ domain, and to determine the role of nonsense-mutation sequence context in rescuing the DMD phenotype by altered mRNA splicing. The long term goal is to determine potential novel therapeutic pathways by improving understanding of muscular dystrophy pathogenesis and dystrophin function.
- Flanigan KM, Ceco E, Lamar KM, Kaminoh Y, Dunn DM, Mendell JR, King WM, Pestronk A, Florence JM, Mathews KD, Finkel RS, Swoboda KJ, Gappmaier E, Howard MT, Day JW, McDonald C, McNally EM, Weiss RB; United Dystrophinopathy Project. (2012) LTBP4 genotype predicts age of ambulatory loss in duchenne muscular dystrophy. Ann Neurol. 2012 Nov 26.
- Flanigan KM. (2012) The muscular dystrophies. Semin Neurol. Jul;32(3):255-63.
Taylor LE, Kaminoh YJ, Rodesch CK, Flanigan KM. (2012) Quantification of dystrophin immunofluorescence in dystrophinopathy muscle specimens. Neuropathol Appl Neurobiol. (2012) Oct;38(6):591-601.
- Mendell JR, Shilling C, Leslie ND, Flanigan KM, al-Dahhak R, Gastier-Foster J, Kneile K, Dunn DM, Duval B, Aoyagi A, Hamil C, Mahmoud M, Roush K, Bird L, Rankin C, Lilly H, Street N, Chandrasekar R, Weiss RB. (2012) Evidence-based path to newborn screening for Duchenne muscular dystrophy. Ann Neurol. 2012 Mar;71(3):304-13.
- Flanigan KM, Dunn DM, von Niederhausern A, Soltanzadeh P, Howard MT, Sampson JB, Swoboda KJ, Bromberg MB, Mendell JR, Taylor LE, Anderson CB, Pestronk A, Florence JM, Connolly AM, Mathews KD, Wong B, Finkel RS, Bonnemann CG, Day JW, McDonald C; United Dystrophinopathy Project Consortium, Weiss RB. (2011) Nonsense mutation-associated Becker muscular dystrophy: interplay between exon definition and splicing regulatory elements within the DMD gene. Hum Mutat. Mar;32(3):299-308.
- Soltanzadeh P, Friez MJ, Dunn D, von Niederhausern A, Gurvich OL, Swoboda KJ, Sampson JB, Pestronk A, Connolly AM, Florence JM, Finkel RS, Bönnemann CG, Medne L, Mendell JR, Mathews KD, Wong BL, Sussman MD, Zonana J, Kovak K, Gospe SM Jr, Gappmaier E, Taylor LE, Howard MT, Weiss RB, Flanigan KM. (2010) Clinical and genetic characterization of manifesting carriers of DMD mutations. Neuromuscul Disord. Aug;20(8):499-504.
- Flanigan KM, Dunn DM, von Niederhausern A, Soltanzadeh P, Gappmaier E, Howard MT, Sampson JB, Mendell JR, Wall C, King WM, Pestronk A, Florence JM, Connolly AM, Mathews KD, Stephan CM, Laubenthal KS, Wong BL, Morehart PJ, Meyer A, Finkel RS, Bonnemann CG, Medne L, Day JW, Dalton JC, Margolis MK, Hinton VJ; United Dystrophinopathy Project Consortium, Weiss RB. (2009) Mutational spectrum of DMD mutations in dystrophinopathy patients: application of modern diagnostic techniques to a large cohort. Hum Mutat. Dec;30(12):1657-66.
- Flanigan KM, Dunn DM, von Niederhausern A, Howard MT, Mendell J, Connolly A, Saunders C, Modrcin A, Dasouki M, Comi GP, Del Bo R, Pickart A, Jacobson R, Finkel R, Medne L, Weiss RB. (2009 ) DMD Trp3X nonsense mutation associated with a founder effect in North American families with mild Becker muscular dystrophy. Neuromuscul Disord. Nov;19(11):743-8.
- Gurvich OL, Maiti B, Weiss RB, Aggarwal G, Howard MT, Flanigan KM. (2009) DMD exon 1 truncating point mutations: amelioration of phenotype by alternative translation initiation in exon 6. Hum Mutat. Apr;30(4):633-40.
- Butterfield RJ, Ramachandran D, Hasstedt SJ, Otterud BE, Leppert MF, Swoboda KJ, Flanigan KM. (2009) A novel form of juvenile recessive ALS maps to loci on 6p25 and 21q22. Neuromuscul Disord. Apr;19(4):279-87.
- Gurvich OL, Tuohy TM, Howard MT, Finkel RS, Medne L, Anderson CB, Weiss RB, Wilton SD, Flanigan KM. (2008) DMD pseudoexon mutations: splicing efficiency, phenotype, and potential therapy. Ann Neurol. Jan;63(1):81-9.
- Lawson VH, Graham BV, Flanigan KM. (2005) Clinical and electrophysiologic features of CMT2A with mutations in the mitofusin 2 gene. Neurology. Jul 26;65(2):197-204.
- Dent KM, Dunn DM, von Niederhausern AC, Aoyagi AT, Kerr L, Bromberg MB, Hart KJ, Tuohy T, White S, den Dunnen JT, Weiss RB, Flanigan KM. (2005) Improved molecular diagnosis of dystrophinopathies in an unselected clinical cohort. Am J Med Genet A. Apr 30;134(3):295-8.