- Assistant Professor
Molecular & Human Genetics
Baylor College of Medicine
Houston, Texas United States
- Adult Genetics Clinic (Clinic)
Baylor College of Medicine - McNair Campus
7200 Cambridge St
Houston, TX 77030
Phone: (713) 798-7764
- Board Certification
- American Board of Internal Medicine
- Board Certification
- American Board of Medical Genetics and Genomics
Honors & Awards
- Chao Physician-Scientist Award
- Ting Tsung and Wei Fong Chao Foundation
- BCM "That's the Way" Award
Professional StatementAs a physician-scientist and a medical and human geneticist, my ultimate goal is to be able to translate our understanding of the relationship between an individual’s genotype and phenotype into actionable and treatable information in the clinic. The first step toward this goal is the elucidation of the complex relationships between genotypes and human disease phenotypes. My research program is focused on the following three scientific inquiries, each of which will lead to a more precise understanding of these relationships:
1. What is the genetic etiology of Postural Orthostatic Tachycardia Syndrome (POTS), and to what extent do genetic heterogeneity and more complex modes of inheritance play a role in the clinical expression of POTS?
POTS represents one of many adolescent- or adult-onset conditions for which the molecular contribution – and genetic architecture – of disease is not well understood (Posey et al., 2016). Despite numerous examples of families with POTS following an autosomal dominant mode of inheritance, candidate disease genes have not been forthcoming, supporting the possibility that genetic heterogeneity, or perhaps more complex modes of inheritance, may play a role in the clinical expression of this condition. To address this possibility, we have built a cohort of individuals and families with POTS and other forms of autonomic dysfunction and are applying and analyzing genomic methods to identify the molecular etiologies of disease in these individuals.
2. How common are dual molecular diagnoses, and can we take advantage of structured phenotype data to predict which individuals with rare conditions are more likely to have two (or more) molecular diagnoses contributing to disease expression?
Dual or multiple, molecular diagnoses break from the ‘one-gene-one-disease’ paradigm, resulting in two or more independently segregating Mendelian conditions within an individual. Despite being long-recognized to occur in ‘rare’ cases, the true frequency of multiple molecular diagnoses has only more recently been described with the emergence of genome-wide techniques, such as array comparative genomic hybridization (aCGH) and ES, enabling a comprehensive identification of rare variation. In collaboration with the BG diagnostic laboratory and the BHCMG, we demonstrated that multiple molecular diagnoses are identified in at least 4.9% of individuals for whom ES is diagnostic (Posey, Harel, et al., 2017). We are now expanding this cohort and utilizing structured phenotype data to develop methods to predict which individuals may have multiple molecular diagnoses.
3. What are the roles of nuclear and mitochondrial genome variation in the expression of atypical forms of diabetes?
Diabetes has been broadly classified into type 1 diabetes (T1D) associated with auto-immune destruction of the pancreas, and type 2 diabetes (T2D) with adult-onset insulin resistance and/or impaired glucose tolerance. Despite these classifications, approximately 1-4% of individuals < 18 years with diabetes have a monogenic form that is clinically (phenotypically) distinct from T1D and T2D. As a member of the Rare and Atypical DIAbetes NeTwork (RADIANT) consortium, we are applying genomic methods to identify the molecular etiology of rare, monogenic forms of diabetes.
- Assia Batzir N, Posey JE, Song X, Akdemir ZC, Rosenfeld JA, Brown CW, Chen E, Holtrop SG, Mizerik E, Nieto Moreno M, Payne K, Raas-Rothschild A, Scott R, Vernon HJ, Zadeh N; Baylor-Hopkins Center for Mendelian Genomics, Lupski JR, Sutton VR "Phenotypic expansion of POGZ-related intellectual disability syndrome (White-Sutton syndrome).." Am J Med Genet A. 2020 Jan;182(1):38-52. Pubmed PMID: 31782611
- Assia Batzir N, Kishor Bhagwat P, Larson A, Coban Akdemir Z, (...); Baylor-Hopkins Center for Mendelian Genomics, Posey JE, Lupski JR, Beaudet AL, Wangler MF "Recurrent arginine substitutions in the ACTG2 gene are the primary driver of disease burden and severity in visceral myopathy.." Hum Mutat.. 2020 Mar;41(3):641-654. Pubmed PMID: 31769566
- Hansen AW, Murugan M, Li H, Khayat MM, Wang L, (...), Posey JE, Yang Y, Wangler MF, Eng CM, Sutton VR, Lupski JR, Boerwinkle E, Gibbs RA "A Genocentric Approach to Discovery of Mendelian Disorders.." Am J Hum Genet.. 2019 Nov 7;105(5):974-986. Pubmed PMID: 31668702
- Herman I, Jolly A, Du H, Dawood M, Abdel-Salam GMH, (…), Posey JE, Lupski JR "Quantitative dissection of multilocus pathogenic variation in an Egyptian infant with severe neurodevelopmental disorder resulting from multiple molecular diagnoses." Am J Med Genet A.. 2022;188:735-750. Pubmed PMID: 34816580
- Jolly A, Bayram Y, Turan S, Aycan Z, Tos T, (...), Posey JE, Lupski JR "Exome Sequencing of a Primary Ovarian Insufficiency Cohort Reveals Common Molecular Etiologies for a Spectrum of Disease.." J Clin Endocrinol Metab.. 2019 May 1;104:3049-3067. Pubmed PMID: 31042289
- Punetha J, Mackay-Loder L, Harel T, Coban-Akdemir Z, Jhangiani SN, Gibbs RA, Lee I, Terespolsky D, Lupski JR, Posey JE "Identification of a pathogenic PMP2 variant in a multi-generational family with CMT type 1: Clinical gene panels versus genome-wide approaches to molecular diagnosis.." Mol Genet Metab. 2018 Nov;125(3):302-304. Pubmed PMID: 30249361
- Karaca E, Posey JE, Coban Akdemir Z, Pehlivan D, Harel T, Jhangiani SN, Bayram Y, Song X, Bahrambeigi V, Yuregir OO, Bozdogan S, Yesil G, Isikay S, Muzny D, Gibbs RA, Lupski JR "Phenotypic expansion illuminates multilocus pathogenic variation." Genet Med.. 2018 Dec;20(12):1528-1537. Pubmed PMID: 29790871
- Jennifer E. Posey, M.D., Ph.D., Tamar Harel, M.D., Ph.D., Pengfei Liu, Ph.D., et al. "Resolution of Disease Phenotypes Resulting from Multilocus Genomic Variation." N Engl J Med. 2017 Jan 5;376(1):21-31. Pubmed PMID: 27959697
- Posey JE, Martinez R, Lankford JE, Lupski JR, Numan MT, Butler IJ. "Dominant Transmission Observed in Adolescents and Families with Orthostatic Intolerance." Pediatr Neurol. 2017 Jan;66:53-58. Pubmed PMID: 27773421
- Posey JE, Mohrbacher N, Smith JL, Patel A, Potocki L, Breman AM "Triploidy Mosaicism (45,X/68,XX) in an Infant Presenting with Failure to Thrive." Am J Med Genet A. 2016;170(3):694-8. Pubmed PMID: 26566716
- Posey JE, Rosenfeld JA, James RA, Bainbridge M, Niu Z, Wang X, Dhar S, Wiszniewski W, Akdemir ZH, Gambin T, Xia F, Person RE, Walkiewicz M, Shaw CA, Sutton VR, Beaudet AL, Muzny D, Eng CM, Yang Y, Gibbs RA, Lupski JR, Boerwinkle E, Plon SE. "Molecular Diagnostic Experience of Whole-Exome Sequencing in Adult Patients." Genet Med. 2016 Jul;18(7):678-85. Pubmed PMID: 26633545
- Posey JE, Burrage LC, Campeau PM, Lu JT, Eble TN, Kratz L, Schlesinger AE, Gibbs RA, Lee BH, Nagamani SC "Adult presentation of X-linked Conradi-Hunermann-Happle syndrome." Am J Med Genet A. 2015 Jun;167(6):1309-14. Pubmed PMID: 25846959
- Posey JE, Burrage LC, Miller MJ, Liu P, Hardison MT, Elsea SH, Sun Q, Yang Y, Willis AS, Schlesinger AE, Bacino CA, and Lee BH "Lysinuric Protein Intolerance Presenting with Multiple Fractures." Mol Genet Metab Rep. 2014;1:176-183. Pubmed PMID: 25419514
- American Society of Human Genetics
- American College of Physicians
- American College of Medical Genetics
- Individual Genomic Analyses to Discover the Molecular Basis and Mechanisms Contributing to Adult-Onset Disease - #K08 HG008986 Grant funding from National Human Genome Research Institute (NHGRI)
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