Frank Probst, M.D., Ph.D.
Assistant Professor of Molecular and Human Genetics
M.D., Ph.D., Human Genetics, University of Michigan, 2001
Resident, Pediatrics, Cornell University Medical Center, 2001-2004
Resident, Clinical Genetics, Baylor College of Medicine, 2004-2007
American Board of Medical Genetics: Clinical Genetics (2007-Present)
Member, American College of Medical Genetics (2005-Present)
Member, American Society of Human Genetics (2004-Present)
Member, American Academy of Pediatrics (2004-Present)
X-linked disorders, X-linked mental retardation, familial multiple lipomatosis
The primary focus of my laboratory is the use of the house mouse (Mus musculus) as a model system for human genetic disorders. We are currently usually a novel breeding scheme to generate mouse models for human X-linked genetic diseases. Male mice are injected with the chemical "supermutagen" N-ethyl-N-nitrosourea (ENU) and then bred to female mice that have only one (as opposed to the usual two) X chromosome. Of the resulting progeny, some of the animals will have inherited a mutagenized X chromosome from their father and no second sex chromosome from their mother. These animals will manifest the results of any X-linked recessive mutations that were caused by the ENU. Such animals are all subjected to a rigorous phenotyping screen. A number of animals with interesting phenotypes are currently being bred to confirm linkage to the X chromosome.
My laboratory is also engaged in the study of a number of other interesting phenotypes in both mice and humans. In the first project, we are characterizing the mouse nse5 (neurosensory 5) mutation. This autosomal recessive trait causes hearing impairment in mice and is a potential model for human deafness. Thus far, we have identified a promising candidate gene for this trait and have confirmed that a small 20 kilobase transgene containing this gene can rescue the mutant phenotype. Ongoing studies will characterize the role of this gene in the normal functioning of the inner ear. In the second project, we are characterizing and mapping an autosomal recessive mouse mutation for spondylocostal dysostosis.
Finally, we are performing linkage studies in an attempt to localize the human gene for familial multiple lipomatosis.
- Boles MK, Wilkinson BM, Wilming LG, Liu B, Probst FJ, Harrow J, Grafham D, Hentges KE, Woodward LP, Maxwell A, Mitchell K, Risley MD, Johnson R, Hirschi K, Lupski JR, Funato Y, Miki H, Marin-Garcia P, Matthews L, Coffey AJ, Parker A, Hubbard TJ, Rogers J, Bradley A, Adams DJ, Justice MJ (2009). Discovery of Candidate Disease Genes in ENU-Induced Mouse Mutants by Large-Scale Sequencing, Including a Splice-Site Mutation in Nucleoredoxin. PLoS Genet. 5(12): e1000759. PubMed PMID: 20011118
- Probst FJ, Cooper ML, Cheung SW, Justice MJ (2008). Genotype, phenotype, and karyotype correlation in the XO mouse model of Turner Syndrome. J. Hered. 99(5): 512-7. PubMed PMID: 18499648
- Probst FJ, Roeder ER, Enciso VB, Ou Z, Cooper ML, Eng P, Li J, Gu Y, Stratton RF, Chinault AC, Shaw CA, Sutton VR, Cheung SW, Nelson DL (2007). Chromosomal microarray analysis (CMA) detects a large X chromosome deletion including FMR1, FMR2, and IDS in a female patient with mental retardation. Am. J. Med. Genet. A. 143A(12): 1358-65. PubMed PMID: 17506108
- Probst FJ, Hedera P, Sclafani AM, Pomponi MG, Neri G, Tyson J, Douglas JA, Petty EM, Martin DM (2004). Skewed X-inactivation in carriers establishes linkage in an X-linked deafness-mental retardation syndrome. Am. J. Med. Genet. A. 131(2): 209-12. PubMed PMID: 15389700
- Martin DM, Probst FJ, Camper SA, Petty EM (2000). Characterisation and genetic mapping of a new X linked deafness syndrome. J. Med. Genet. 37(11): 836-41. PubMed PMID: 11073537
- Probst FJ, Camper SA (1999). The role of mouse mutants in the identification of human hereditary hearing loss genes. Hear. Res. 130(1-2): 1-6. PubMed PMID: 10320095
- Probst FJ, Chen KS, Zhao Q, Wang A, Friedman TB, Lupski JR, Camper SA (1999). A physical map of the mouse shaker-2 region contains many of the genes commonly deleted in Smith-Magenis syndrome (del17p11.2p11.2). Genomics 55(3): 348-52. PubMed PMID: 10049592
- Wang A, Liang Y, Fridell RA, Probst FJ, Wilcox ER, Touchman JW, Morton CC, Morell RJ, Noben-Trauth K, Camper SA, Friedman TB (1998). Association of unconventional myosin MYO15 mutations with human nonsyndromic deafness DFNB3. Science 280(5368): 1447-51. PubMed PMID: 9603736
- Probst FJ, Fridell RA, Raphael Y, Saunders TL, Wang A, Liang Y, Morell RJ, Touchman JW, Lyons RH, Noben-Trauth K, Friedman TB, Camper SA (1998). Correction of deafness in shaker-2 mice by an unconventional myosin in a BAC transgene. Science 280(5368): 1444-7. PubMed PMID: 9603735
Frank Probst, M.D., Ph.D.
Department of Molecular and Human Genetics
Baylor College of Medicine
One Baylor Plaza, Rm. R807
Mail Stop: BCM225
Houston, TX, 77030, U.S.A.