Ophthalmic genetics

MSc: Andhra University, India.

PhD: All India Institute of Medical Sciences, New Delhi, India.

Fellowship: Harvard Medical School.

Certification: Clinical Molecular Genetics, 2007.

Kopplin LJ, Igo RP Jr, Wang Y, Sivakumaran TA, Hagstrom SA, Peachey NS, Francis PJ, Klein ML, SanGiovanni JP, Chew EY, Pauer GJ, Sturgill GM, Joshi T, Tian L, Xi Q, Henning AK, Lee KE, Klein R, Klein BE, Iyengar SK. Genome-wide association identifies SKIV2L and MYRIP as protective factors for age-related macular degeneration. Genes Immun. 2010 Dec;11(8):609-21.

Ikram MK, Sim X, Jensen RA, Cotch MF, Hewitt AW, Ikram MA, Wang JJ, Klein R, Klein BE, Breteler MM, Cheung N, Liew G, Mitchell P, Uitterlinden AG, Rivadeneira F, Hofman A, de Jong PT, van Duijn CM, Kao L, Cheng CY, Smith AV, Glazer NL, Lumley T, McKnight B, Psaty BM, Jonasson F, Eiriksdottir G, Aspelund T; Global BPgen Consortium, Harris TB, Launer LJ, Taylor KD, Li X, Iyengar SK, Xi Q, Sivakumaran TA, Mackey DA, Macgregor S, Martin NG, Young TL, Bis JC, Wiggins KL, Heckbert SR, Hammond CJ, Andrew T, Fahy S, Attia J, Holliday EG, Scott RJ, Islam FM, Rotter JI, McAuley AK, Boerwinkle E, Tai ES, Gudnason V, Siscovick DS, Vingerling JR, Wong TY. Genetic determinants for retinal microcirculation: Genome-wide association study from the CHARGE consortium. PLoS Genet. 2010 Oct 28;6(10):e1001184.

SanGiovanni JP, Arking DE, Iyengar SK, Elashoff M, Clemons TE, Reed GF, Henning AK, Sivakumaran TA, Xu X, DeWan A, Agrón E, Rochtchina E, Sue CM, Wang JJ, Mitchell P, Hoh J, Francis PJ, Klein ML, Chew EY, Chakravarti A. Mitochondrial DNA variants of respiratory complex I that uniquely characterize haplogroup T2 are associated with increased risk of age-related macular degeneration. PLoS One. 2009;4(5):e5508.

Wang JJ, Rochtchina E, Smith W, Klein R, Klein BE, Joshi T, Sivakumaran TA, Iyengar S, Mitchell P. Combined effects of complement factor H genotypes, fish consumption, and inflammatory markers on long-term risk for age-related macular degeneration in a cohort. Am J Epidemiol. 2009 Mar 1;169(5):633-41.

Robertson NG, Jones SM, Sivakumaran TA, Giersch AB, Jurado SA, Call LM, Miller CE, Maison SF, Liberman MC, Morton CC. A targeted Coch missense mutation: a knock-in mouse model for DFNA9 late-onset hearing loss and vestibular dysfunction. Hum Mol Genet. 2008 Nov 1;17(21):3426-34.

Ruel J, Emery S, Nouvian R, Bersot T, Amilhon B, Van Rybroek JM, Rebillard G, Lenoir M, Eybalin M, Delprat B, Sivakumaran TA, Giros B, El Mestikawy S, Moser T, Smith RJ, Lesperance MM, Puel JL. Impairment of SLC17A8 encoding vesicular glutamate transporter-3, VGLUT3, underlies nonsyndromic deafness DFNA25 and inner hair cell dysfunction in null mice. Am J Hum Genet. 2008 Aug;83(2):278-92.

Edwards AO, Chen D, Fridley BL, James KM, Wu Y, Abecasis G, Swaroop A, Othman M, Branham K, Iyengar SK, Sivakumaran TA, Klein R, Klein BE, Tosakulwong N. Toll-like receptor polymorphisms and age-related macular degeneration. Invest Ophthalmol Vis Sci. 2008 Apr;49(4):1652-9.

Xing C, Sivakumaran TA, Wang JJ, Rochtchina E, Joshi T, Smith W, Mitchell P, Iyengar SK. Complement factor H polymorphisms, renal phenotypes and age-related macular degeneration: the Blue Mountains Eye Study. Genes Immun. 2008 Apr;9(3):231-9.

Sivakumaran TA, Resendes BL, Robertson NG, Giersch AB, Morton CC. Characterization of an abundant COL9A1 transcript in the cochlea with a novel 3' UTR: Expression studies and detection of miRNA target sequence. J Assoc Res Otolaryngol. 2006 Jun;7(2):160-72.

Sivakumaran TA, Shen P, Wall DP, Do BH, Kucheria K, Oefner PJ. Conservation of the RB1 gene in human and primates. Hum Mutat. 2005 Apr;25(4):396-409.

Clinical Interests

Connective tissue disorders and skeletal dysplasia; interventional genetics; molecular genetics

Research Interests

Management of connective tissue disorders; natural history of Ehlers-Danlos syndrome; clinical trials; discovery of new causative genes in connective tissue disorders 

PhD: George Washington University, Washington, DC, 1995.

MD: Indiana University, Indianapolis, IN, 1999.

Residency: Pediatrics / Human Genetics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, 2004.

Fellowship: Clinical Molecular Genetics, Cincinnati Children's Hospital Medical Center, 2006.

Certification: Pediatrics, 2003; Clinical Genetics, 2005; Clinical Molecular Genetics, 2007.

Bendik EM, Tinkle BT, Al-Shuik E, Levin L, Martin A, Thaler R, Atzinger CL, Rueger J, Martin VT. Joint hypermobility syndrome: A common clinical disorder associated with migraine in women. Cephalalgia. 2011 Feb 2.

Sun GH, Samy RN, Tinkle BT, Cornelius RS, Brown DK. Craniometaphyseal dysplasia-induced hearing loss. Otol Neurotol. 2011 Feb;32(2):e9-10. 

Atzinger CL, Meyer RA, Khoury PR, Gao Z, Tinkle BT. Cross-Sectional and Longitudinal Assessment of Aortic Root Dilation and Valvular Anomalies in Hypermobile and Classic Ehlers-Danlos Syndrome. J Pediatr. 2010 Dec 28. 

Z Yazici, B Kline-Fath, T Laor,BT Tinkle.  Fetal MR imaging of Kniest dysplasia.  Pediatr Radiol. 2010 Mar;40(3):348-52.

Tinkle BT,Bird HA, Grahame R, Lavallee M, Levy HP, Sillence D. The lack of clinical distinction between the hypermobility type of Ehlers-Danlos syndrome and the joint hypermobility syndrome (a.k.a. hypermobility syndrome). Am J Med Genet. 2009 Nov;149A(11):2368-70.  

 Zarate YA, Mena R, Martin LJ, Steele P, Tinkle BT, Hopkin RJ. Experience with hemihyperplasia and Beckwith-Wiedemann syndrome surveillance protocol. Am J Med Genet A. 2009 Aug;149A(8):1691-7.

M Ednick, BT Tinkle, J Phromchairak, J Egelhoff, R Amin, N Simakajornboon. Sleep-related respiratory abnormalities and arousal pattern in achondroplasia during early infancy period. J Pediatr. 2009;155(4):510-5.

Mattheis PJ, Hickey F, Tinkle BT, Hopkin R:  Prenatal diagnosis: beyond decisions about termination. J Pediatr. 2008 Nov;153(5):728.

Burrow TA, Hopkin RJ, Leslie ND, Tinkle BT, Grabowski GA. Enzyme reconstitution/replacement therapy for lysosomal storage diseases. Curr Opin Pediatr. 2007 Dec;19(6):628-35.

Sutherell J, Zarate Y, Tinkle BT, Markham LW, Cripe LH, Hyland JC, Witte D, Hopkin RJ, Hinton RB. Novel fibrillin 1 mutation in a case of neonatal Marfan syndrome: the increasing importance of early recognition. Congenit Heart Dis. 2007 Sep;2(5):342-6. 

Clinical Interests

Molecular genetics diagnosis of inherited immunodeficiency disorders and other genetic conditions

Research Interests

Molecular defects and molecular diagnosis of primary immunodeficiency diseases; Genetic aspects of predictive personalized medicine (pharmacogenetics)

MD: Tianjin Medical University, Tianjin, China, 1993

MBA: University of Cincinnati, College of Business Administration, 2001

Residency: Gong'an Hospital, Tianjin, China, 1993-1995

Fellowship: Clinical Molecular Genetics Fellow, Division of Human Genetics, Cincinnati Children's Hospital, 2002-2004

Zhang K, Jordan MB, Klein P, Villanueva J, Risma K, Filipovic AH. .Hypomorphic mutations in PRF1, MUNC13-4, and STXBP2 are associated with adult-onset familial hemophagocytic lymphohistiocytosis.Blood. 2011 August 31.

Filipovich AH, Zhang K, Snow AL, Marsh RA. X-linked lymphoproliferative syndromes: brothers or distant cousins? Blood. 2010 Nov 4;116(18):3398-408.

Marsh RA, Madden L, Kitchen BJ, Mody R, McClimon B, Jordan MB, Bleesing JJ, Zhang K, Filipovich AH. XIAP deficiency: a unique primary immunodeficiency best classified as X-linked familial hemophagocytic lymphohistiocytosis and not as X-linked lymphoproliferative disease. Blood. 2010 Aug 19;116(7):1079-82. 

Marsh RA, Satake N, Biroschak J, Jacobs T, Johnson J, Jordan MB, Bleesing JJ, Filipovich AH, Zhang K. STX11 mutations and clinical phenotypes of familial hemophagocytic lymphohistiocytosis in North America. Pediatr Blood Cancer. 2010 Jul 15;55(1):134-40.

Pestian J, Spencer M, Matykiewicz P, Zhang K, Vinks AA, Glauser T. Personalizing Drug Selection Using Advanced Clinical Decision Support. Biomed Inform Insights. 2009 Jun 23;2:19-29.

Prows CA, Nick TG, Saldaña SN, Pathak S, Liu C, Zhang K, Daniels ZS, Vinks AA, Glauser TA. Drug-metabolizing enzyme genotypes and aggressive behavior treatment response in hospitalized pediatric psychiatric patients. J Child Adolesc Psychopharmacol. 2009 Aug;19(4):385-94.

Marsh RA, Villanueva J, Kim MO, Zhang K, Marmer D, Risma KA, Jordan MB, Bleesing JJ, Filipovich AH. Patients with X-linked lymphoproliferative disease due to BIRC4 mutation have normal invariant natural killer T-cell populations. Clin Immunol. 2009 Jul;132(1):116-23.

Marsh RA, Villanueva J, Zhang K, Snow AL, Su HC, Madden L, Mody R, Kitchen B, Marmer D, Jordan MB, Risma KA, Filipovich AH, Bleesing JJ. A rapid flow cytometric screening test for X-linked lymphoproliferative disease due to XIAP deficiency. Cytometry B Clin Cytom. 2009 Sep;76(5):334-44.

Prausa SE, Fukuda T, Maseck D, Curtsinger KL, Liu C, Zhang K, Nick TG, Sherbotie JR, Ellis EN, Goebel J, Vinks AA. UGT genotype may contribute to adverse events following medication with mycophenolate mofetil in pediatric kidney transplant recipients. Clin Pharmacol Ther. 2009 May;85(5):495-500.

Zhang K, Biroschak J, Glass DN, Thompson SD, Finkel T, Passo MH, Binstadt BA, Filipovich A, Grom AA. Macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis is associated with MUNC13-4 polymorphisms. Arthritis Rheum. 2008 Sep;58(9):2892-6.

BS: Genetics, University of Wisconsin Madison, Madison, WI, 2009

MS: Genetic Counseling, University of Cincinnati, Cincinnati, OH, 2011

Barriers to genetic counseling;  innovative methods of providing complex genetic information to patients and physicians

MS: Medical Genetics, Indiana University, Indianapolis, IN, 1985.

MS: Clinical Behavioral Psychology, Eastern Michigan University, Ypsilanti, MI, 1995.

Certification: Genetic Counseling, 1987; Project Management, 2010

Zhang K, Jordan MB, Marsh RA, Johnson JA, Kissell D, Meller J, Villanueva J, Risma KA, Wei Q, Klein PS, Filipovich AH. Hypomorphic mutations in PRF1, MUNC13-4, and STXBP2 are associated with adult-onset familial hemophagocytic lymphohistiocytosis. Blood. 2011 Aug 31.

Bleesing JJH,  Johnson J, Zhang K. Autoimmune Lymphoproliferative Syndrome.GeneReviews at GeneTests: Medical Genetics Information Resource [database online]. Copyright, University of Washington, Seattle, 1997-2010.

Filipovich AH, Johnson J, Zhang K. WAS-Related Disorders.GeneReviews at GeneTests: Medical Genetics Information Resource [database online]. Copyright, University of Washington, Seattle, 1997-2010.

Marsh RA, Satake N, Biroschak J, Jacobs T, Johnson J, Jordan MB, Bleesing JJ, Filipovich AH, Zhang K STX11 mutations and clinical phenotypes of familial hemophagocytic lymphohistiocytosis in North America.  Pediatr Blood Cancer. 2010. 55(1):134-40.

Zhang K, Filipovich AH, Johnson J, Marsh RA, Villanueva J.  Hemophagocytic Lymphohistiocytosis, Familial. GeneReviews at GeneTests: Medical Genetics Information Resource [database online]. Copyright, University of Washington, Seattle, 1997-2011.

Johnson J, Filipovich AH, Zhang K.  X-Linked Hyper IgM Syndrome.GeneReviews at GeneTests: Medical Genetics Information Resource [database online]. Copyright, University of Washington, Seattle, 1997-2011.

Sumegi J, Johnson J, Filipovich A, Zhang K, Marsh R.  Lymphoproliferative Disease, X-Linked.GeneReviews at GeneTests: Medical Genetics Information Resource [database online]. Copyright, University of Washington, Seattle, 1997-2011. 

Zhang K, Johnson JA, Biroschak J, Villanueva J, Lee SM, Bleesing JJ, Risma KA, Wenstrup RJ, Filipovich AH.  Familial haemophagocytic lymphohistiocytosis in patients who are heterozygous for the A91V perforin variation is often associated with other genetic defects.  Int J Immunogenet. 2007 Aug;34(4):231-3

MS: University of Cincinnati, Cincinnati, OH, 2001.

Certification: American Board of Genetic Counseling, 2002.

Martin, LJ, Ramachandran, V, Cripe LH, Hinton RB, Andelfinger G, Tabangin M, Shooner K, Keddache M, Benson DW. Evidence in favor of linkage to human chromosomal regions 18q, 5q, and 13q for bicuspid aortic valve and associated cardiovascular malformations. Hum Genet. 2007;121:275-84.

Shooner KA, Rope AF, Hopkin RJ, Andelfinger GU, Benson DW. Genetic analyses in two extended families with deletion 22q11 syndrome: importance of extracardiac manifestations. J Pediatr. 2005 Mar;146(3):382-7.

Beery TA, Shooner KA. Family history: the first genetic screen. Nurse Practitioner. 2004;29(11)14-23.

Cripe L, Andelfinger G, Martin LJ, Shooner K, Benson DW. Bicuspid aortic valve is heritable. J Amer Coll Cardiol 2004;44(1):138-43.

Howell KA, Huelsman KM, Everett JN, Hopkin RJ. Breast cancer genetics education for college women: an evaluation of approaches. J Cancer Educ. 2002 Summer;17(2):4-77.