LMNA gene and its involvement in Hutchinson-Gilford Progeria...

Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid

Reexamination Certificate

Rate now

  [ 0.00 ] – not rated yet Voters 0   Comments 0

Details

C536S023100

Reexamination Certificate

active

08034557

ABSTRACT:
Disclosed herein are point mutations in the LMNA gene that cause HGPS. These mutations activate a cryptic splice site within the LMNA gene, which leads to deletion of part of exon 11 and generation of a mutant Lamin A protein product that is 50 amino acids shorter than the normal protein. In addition to the novel Lamin A variant protein and nucleic acids encoding this variant, methods of using these molecules in detecting biological conditions associated with a LMNA mutation in a subject (e.g., HGPS, arteriosclerosis, and other age-related diseases), methods of treating such conditions, methods of selecting treatments, methods of screening for compounds that influence Lamin A activity, and methods of influencing the expression of LMNA or LMNA variants are also described. Oligonucleotides and other compounds for use in examples of the described methods are also provided, as are protein-specific binding agents, such as antibodies, that bind specifically to at least one epitope of a Lamin A variant protein preferentially compared to wildtype Lamin A, and methods of using such antibodies in diagnosis, treatment, and screening. Also provided are kits for carrying out the methods described herein.

REFERENCES:
patent: 6060038 (2000-05-01), Burns et al.
patent: 6342487 (2002-01-01), Riou et al.
patent: 6737410 (2004-05-01), Doherty et al.
patent: 2002/0044941 (2002-04-01), Rosen et al.
patent: 2002/0098495 (2002-07-01), Burmer et al.
patent: 2003/0125326 (2003-07-01), Rybak
patent: 2004/0110769 (2004-06-01), End
patent: WO 97/30053 (1997-08-01), None
patent: WO 01/64218 (2001-09-01), None
patent: WO 02/04662 (2002-01-01), None
,Stoneking et al. (Am. J. Hum. Genet. 48:370-382, 1991.
Adjei et al., “Comparison of Potential Markers of Farnesyl Transferase Inhibition,”Clinical Cancer Res., 6:2318-2325 (Jun. 2000).
Bonne et al., “Clinical and Molecular Genetic Spectrum of Autosomal Dominant Emery-Dreifuss Muscular Dystrophy due to Mutations of the Lamin A/C Gene,” Annals of Neurology (Aug. 2000), vol. 48, No. 2, 170-180.
Bonne et al., “Mutations in the gene encoding lamin A/C cause autosomal dominant Emery-Dreifuss muscular dystrophy,” Nature Genetics (Mar. 1999), vol. 21, No. 3, 285-288.
Burke and Stewart, “Life at the Edge: The Nuclear Envelope and Human Disease,”Molecular Cell Biology—Nature Reviews3:575-585 (Aug. 2002).
Cao and Hegele, “LMNAis mutated in Hutchinson-Gilford progeria (MIM 176670) but not in Wiedemann-Rautenstrauch progeroid syndrome (MIM 264090),”J. Hum. Genet48:271-274 (2003).
Cohen et al., “Inhibitors of Prenylation of Ras and Other G-proteins and Their Application as Therapeutics,”Biochem. Pharm., 60:1061-1068 (2000).
Cox and Der, “Farnesyltransferase inhibitors: promises and realities,”Curr. Opin. Pharm. 2:388-393 (2002).
De Sandre-Giovannoli et al., “Homozygous Defects in LMNA, Encoding Lamin A/C Nuclear-Envelope Proteins, Cause Autosomal Recessive Axonal Neuropathy in Human (Charcot-Marie-Tooth Disorder Type 2) and Mouse,” Am. J. Hum. Genet. (2002), vol. 70, No. 3, 726-736.
De Sandre-Giovannoli, et al., “Lamin A Truncation in Hutchinson-Gilford Progeria,”Science300(4):2055 (Jun. 27, 2003).
Delahunt et al., “Progeria kidney has abnormal mesangial collagen distribution,”Pediatr. Nephrol. 15:279-285 (2000).
Eriksson et al., “Recurrentde novopoint mutations in lamin A cause Hutchinson-Gilford Progeria Syndrome,”Nature423:293-298 (May 15, 2003).
Faivre et al., “Can Hutchinson-Gilford Progeria Syndrome be a Neonatal Condition?”Letter to the Editor—Am. J. Med. Genet. 87:450-452 (1999).
Fisher et al., “cDNA sequencing of nuclear lamins A and C reveals primary and secondary structural homology to intermediate filament proteins,”Proc. Natl. Acad. Sci. USA83:6450-6454 (Sep. 1986).
Fong et al., “Heterozygosity forLmnadeficiency eliminates the progeria-like phenotypes inZmpste24-deficient mice,”Proc. Natl. Sci. Acad. USA101(52)18111-18116 (Dec. 28, 2004).
Garcia et al., “Peptidomimetic Inhibitors of Ras Farnesylation and Function in Whole Cells,”J. Biol. Chem., 268(25):18415-18418 (1993).
Genschel et al., “Mutations in the LMNA Gene Encoding Lamin A/C,” Human Mutation (2000), vol. 16, No. 6, 451-459.
Goldman et al., “Accumulation of mutant lamin A causes progressive changes in nuclear architecture in Hutchinson-Gilford progeria syndrome,” 101(24):8963-8968 (Jun. 15, 2004).
Ha et al., “Cardiovascular Findings of Hutchinson-Gilford Syndrome—A Doppler and two-dimensional Echocardiographic study--,”Yonset Med. J. 34(4):352-355 (1993).
Hegele et al., “Common Genomic Variation in LMNA Modulates Indexes of Obesity in Inuit,” J. of Clinical Endocrinology and Metabolism (2001), vol. 86, No. 6, 2747-2751.
Hegele, “Premature Atherosclerosis Associated with Monogenic Insulin Resistance,”Circulation—Clinical Invest. and Rep. 2225-2229 (May 8, 2001).
Hegele, “Premature Atherosclerosis Associated with Monogenic Insulin Resistance,” Circulation (2001), vol. 103, No. 18, 2225-2229.
Henig, “Racing with Sam,”The New York Times Magazine, 46-51 (Jan. 30, 2005).
Hoeffel et al., “Mandibulo-acral dysplasia,”Skeletal Radiol. 29:668-671 (2000).
Hoover et al., “Overcoming STI571 resistance with the farnesyl transferase inhibitor SCH66336,”Blood, 100(3):1068-1071 (Aug. 1, 2002).
Hutchinson, “Lamins: Building Blocks or Regulators of Gene Expression?”Molecular Cell Biology3(11):848-858 (Nov. 2002).
Ikeda and Shimada, Pleiotropic Effects of Statins on the Vascular Tissue,Current Drug Targets—Cardiovascular&Haematological Disorders, 51-58 (2001).
Jansen and Romiti, “Progeria Infantum (Hutchinson-Gilford Syndrome) Associated with Scleroderma-Like Lesions and Acro-Osteolysis: A Case Report and Brief Review of the Literature,”Pediatric Dermatology17(4):282-285 (2000).
Lutz et al., “Nucleoplasmic localization of prelamin A: Implications for prenylation-dependent lamin A assembly into the nuclear lamina,”Proc. Natl. Acad. Sci. USA89:3000-3004 (Apr. 1992).
Ly et al., “Mitotic Misregulation and Human Aging,”Science287:2486.
Machiels et al., “An Alternative Splicing Product of the Lamin A/C Gene Lacks Exon 10,” J. of Biological Chemistry (1996), vol. 271, No. 16, 9249-9253.
Maske et al., “A carboxyl-terminal interaction of lamin B1 is dependent on the CAAX endoprotease Rcel and carboxymethylation,”J. Cell Biol., 162(7):1223-1232 (Sep. 29, 2003).
McKeon et al., “Homologies in both primary and secondary structure between nuclear envelope and intermediate filament proteins,”Nature319:463-468 (Feb. 6, 1986).
Mégnin-Chanet et al., “The farnesyl transferase inhibitor RPR-130401 does not alter radiation susceptibility in human tumor cells with a K-Ras mutation in spite of large changes in ploidy and lamin B distribution,”BMC Pharm. 2:2 (2002).
Nalbone et al., “Statins: Maid-of-all-work in Cardiovascular Dieseases!”Archives Des Maladies Du Coeur Et Des Vaisseaux, 96(3):207-213 (Mar. 2003).
Novelli et al., “Mandibuloacral Dysplasia is Caused by a Mutation inLMNA-Encoding Lamin A/C,”Am. J. Hum. Genet., 71:426-431 (2002).
Pesce and Rothe, “The Premature Aging Syndromes,”Clinics in Dermatology14:161-170 (1996).
Peters et al., “Activity of the farnesyl protein transferase inhibitor SCH66336 against BCR/ABL-induced murine leukemia and primary cells from patients with chronic myeloid leukemia,”Blood97(5):1404-1412 (Mar. 1, 2001).
Pollex et al., “Hutchinson-Gilford progeria syndrome,”Clin.. Genet., 66:375-381 (2004).
Rodríguez and Pérez-Alonso, “Diagnosis of Progeria Syndrome is the Only One Possible,”Letter to the Editor—Am. J. Med. Genet., 87:453-4

LandOfFree

Say what you really think

Search LandOfFree.com for the USA inventors and patents. Rate them and share your experience with other people.

Rating

LMNA gene and its involvement in Hutchinson-Gilford Progeria... does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with LMNA gene and its involvement in Hutchinson-Gilford Progeria..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and LMNA gene and its involvement in Hutchinson-Gilford Progeria... will most certainly appreciate the feedback.

Rate now

     

Profile ID: LFUS-PAI-O-4283527

  Search
All data on this website is collected from public sources. Our data reflects the most accurate information available at the time of publication.