Suma Shankar | University of California, Davis (original) (raw)
Papers by Suma Shankar
Investigative Ophthalmology & Visual Science, May 10, 2007
Molecular Genetics and Metabolism, 2017
Molecular Genetics and Metabolism, Feb 1, 2016
Molecular Genetics and Metabolism, Feb 1, 2016
Molecular Genetics & Genomic Medicine
American Journal of Ophthalmology Case Reports
American Journal of Medical Genetics Part A, 2022
RASopathies are a group of genetic disorders that are caused by genes that affect the canonical R... more RASopathies are a group of genetic disorders that are caused by genes that affect the canonical Ras/mitogen‐activated protein kinase (MAPK) signaling pathway. Despite tremendous progress in understanding the molecular consequences of these genetic anomalies, little movement has been made in translating these findings to the clinic. This year, the seventh International RASopathies Symposium focused on expanding the research knowledge that we have gained over the years to enhance new discoveries in the field, ones that we hope can lead to effective therapeutic treatments. Indeed, for the first time, research efforts are finally being translated to the clinic, with compassionate use of Ras/MAPK pathway inhibitors for the treatment of RASopathies. This biannual meeting, organized by the RASopathies Network, brought together basic scientists, clinicians, clinician scientists, patients, advocates, and their families, as well as representatives from pharmaceutical companies and the Nationa...
Investigative Ophthalmology & Visual Science, 2007
Annals of translational medicine, 2021
Background Ceroid lipofuscinosis type 8 belongs to a heterogenous group of vision and life-threat... more Background Ceroid lipofuscinosis type 8 belongs to a heterogenous group of vision and life-threatening neurodegenerative diseases, neuronal ceroid lipofuscinosis (NCL). Effective therapy is limited to a single drug for treatment of ceroid lipofuscinosis type 2, necessitating animal disease models to facilitate further therapeutic development. Murine models are advantageous for therapeutic development due to easy genetic manipulation and rapid breeding, however appropriate genetic models need to be identified and characterized before being used for therapy testing. To date, murine models of ocular disease associated with ceroid lipofuscinosis type 8 have only been characterized in motor neuron degeneration mice. Methods Cln8-/- mice were produced by CRISPR/Cas9 genome editing through the International Mouse Phenotyping Consortium. Ophthalmic examination, optical coherence tomography, electroretinography, and ocular histology was performed on Cln8-/- mice and controls at 16 weeks of a...
Investigative Ophthalmology & Visual Science, 2007
Molecular Genetics and Metabolism, 2018
and demographic variables were used as predictors in this model. Optimal clustering and goodness-... more and demographic variables were used as predictors in this model. Optimal clustering and goodness-of-fit were assessed by BIC score. Clusters represented distinct phenotypic groups which aligned with GBA1 mutation and PD status. UPSIT was the best predictor of class status, as expected, providing proof of principle. FSS also predicted cluster well. This is the first use of LCCA and discriminant analysis to identify phenotypic profiles of GBA1 mutation carriers. These methods may help identify at-risk individuals likely to benefit from early therapeutic interventions.
The American Journal of Human Genetics, 2021
Genetic disorders are a leading contributor to mortality in neonatal and pediatric intensive care... more Genetic disorders are a leading contributor to mortality in neonatal and pediatric intensive care units (ICUs). Rapid whole-genome sequencing (rWGS)-based rapid precision medicine (RPM) is an intervention that has demonstrated improved clinical outcomes and reduced costs of care. However, the feasibility of broad clinical deployment has not been established. The objective of this study was to implement RPM based on rWGS and evaluate the clinical and economic impact of this implementation as a first line diagnostic test in the California Medicaid (Medi-Cal) program. Project Baby Bear was a payor funded, prospective, real-world quality improvement project in the regional ICUs of five tertiary care children's hospitals. Participation was limited to acutely ill Medi-Cal beneficiaries who were admitted November 2018 to May 2020, were <1 year old and within one week of hospitalization, or had just developed an abnormal response to therapy. The whole cohort received RPM. There were two prespecified primary outcomes-changes in medical care reported by physicians and changes in the cost of care. The majority of infants were from underserved populations. Of 184 infants enrolled, 74 (40%) received a diagnosis by rWGS that explained their admission in a median time of 3 days. In 58 (32%) affected individuals, rWGS led to changes in medical care. Testing and precision medicine cost 1.7millionandledto1.7 million and led to 1.7millionandledto2.2-2.9 million cost savings. rWGS-based RPM had clinical utility and reduced net health care expenditures for infants in regional ICUs. rWGS should be considered early in ICU admission when the underlying etiology is unclear.
Molecular Genetics and Metabolism, 2019
Low-dose agalsidase beta treatment in male pediatric patients with Fabry disease: A 5-year random... more Low-dose agalsidase beta treatment in male pediatric patients with Fabry disease: A 5-year randomized controlled trial
American Journal of Medical Genetics Part A, 2019
The neurofibromatoses, which include neurofibromatosis type I (NF1), neurofibromatosis type II (N... more The neurofibromatoses, which include neurofibromatosis type I (NF1), neurofibromatosis type II (NF2), and schwannomatosis, are a group of syndromes characterized by tumor growth in the nervous system. The RASopathies are a group of syndromes caused by germline mutations in genes that encode components of the RAS/mitogen‐activated protein kinase (MAPK) pathway. The RASopathies include NF1, Noonan syndrome, Noonan syndrome with multiple lentigines, Costello syndrome, cardio‐facio‐cutaneous syndrome, Legius syndrome, capillary malformation arterio‐venous malformation syndrome, and SYNGAP1 autism. Due to their common underlying pathogenetic etiology, all these syndromes have significant phenotypic overlap of which one common feature include a predisposition to tumors, which may be benign or malignant. Together as a group, they represent one of the most common multiple congenital anomaly syndromes estimating to affect approximately one in 1000 individuals worldwide. The subcontinent of I...
Molecular genetics & genomic medicine, Jan 12, 2018
The p.Asn215Ser or p.N215S GLA variant has been associated with late-onset cardiac variant of Fab... more The p.Asn215Ser or p.N215S GLA variant has been associated with late-onset cardiac variant of Fabry disease. To expand on the scarce phenotype data, we analyzed natural history data from 125 p.N215S patients (66 females, 59 males) enrolled in the Fabry Registry (NCT00196742) and compared it with data from 401 patients (237 females, 164 males) harboring mutations associated with classic Fabry disease. We evaluated interventricular septum thickness (IVST), left ventricular posterior wall thickness (LVPWT), estimated glomerular filtration rate and severe clinical events. In p.N215S males, mildly abnormal mean IVST and LVPWT values were observed in patients aged 25-34 years, and values gradually increased with advancing age. Mean values were similar to those of classic males. In p.N215S females, these abnormalities occurred primarily in patients aged 55-64 years. Severe clinical events in p.N215S patients were mainly cardiac (males 31%, females 8%) while renal and cerebrovascular events...
Molecular Genetics and Metabolism, 2017
Molecular Genetics and Metabolism, 2017
Investigative Ophthalmology & Visual Science, May 10, 2007
Molecular Genetics and Metabolism, 2017
Molecular Genetics and Metabolism, Feb 1, 2016
Molecular Genetics and Metabolism, Feb 1, 2016
Molecular Genetics & Genomic Medicine
American Journal of Ophthalmology Case Reports
American Journal of Medical Genetics Part A, 2022
RASopathies are a group of genetic disorders that are caused by genes that affect the canonical R... more RASopathies are a group of genetic disorders that are caused by genes that affect the canonical Ras/mitogen‐activated protein kinase (MAPK) signaling pathway. Despite tremendous progress in understanding the molecular consequences of these genetic anomalies, little movement has been made in translating these findings to the clinic. This year, the seventh International RASopathies Symposium focused on expanding the research knowledge that we have gained over the years to enhance new discoveries in the field, ones that we hope can lead to effective therapeutic treatments. Indeed, for the first time, research efforts are finally being translated to the clinic, with compassionate use of Ras/MAPK pathway inhibitors for the treatment of RASopathies. This biannual meeting, organized by the RASopathies Network, brought together basic scientists, clinicians, clinician scientists, patients, advocates, and their families, as well as representatives from pharmaceutical companies and the Nationa...
Investigative Ophthalmology & Visual Science, 2007
Annals of translational medicine, 2021
Background Ceroid lipofuscinosis type 8 belongs to a heterogenous group of vision and life-threat... more Background Ceroid lipofuscinosis type 8 belongs to a heterogenous group of vision and life-threatening neurodegenerative diseases, neuronal ceroid lipofuscinosis (NCL). Effective therapy is limited to a single drug for treatment of ceroid lipofuscinosis type 2, necessitating animal disease models to facilitate further therapeutic development. Murine models are advantageous for therapeutic development due to easy genetic manipulation and rapid breeding, however appropriate genetic models need to be identified and characterized before being used for therapy testing. To date, murine models of ocular disease associated with ceroid lipofuscinosis type 8 have only been characterized in motor neuron degeneration mice. Methods Cln8-/- mice were produced by CRISPR/Cas9 genome editing through the International Mouse Phenotyping Consortium. Ophthalmic examination, optical coherence tomography, electroretinography, and ocular histology was performed on Cln8-/- mice and controls at 16 weeks of a...
Investigative Ophthalmology & Visual Science, 2007
Molecular Genetics and Metabolism, 2018
and demographic variables were used as predictors in this model. Optimal clustering and goodness-... more and demographic variables were used as predictors in this model. Optimal clustering and goodness-of-fit were assessed by BIC score. Clusters represented distinct phenotypic groups which aligned with GBA1 mutation and PD status. UPSIT was the best predictor of class status, as expected, providing proof of principle. FSS also predicted cluster well. This is the first use of LCCA and discriminant analysis to identify phenotypic profiles of GBA1 mutation carriers. These methods may help identify at-risk individuals likely to benefit from early therapeutic interventions.
The American Journal of Human Genetics, 2021
Genetic disorders are a leading contributor to mortality in neonatal and pediatric intensive care... more Genetic disorders are a leading contributor to mortality in neonatal and pediatric intensive care units (ICUs). Rapid whole-genome sequencing (rWGS)-based rapid precision medicine (RPM) is an intervention that has demonstrated improved clinical outcomes and reduced costs of care. However, the feasibility of broad clinical deployment has not been established. The objective of this study was to implement RPM based on rWGS and evaluate the clinical and economic impact of this implementation as a first line diagnostic test in the California Medicaid (Medi-Cal) program. Project Baby Bear was a payor funded, prospective, real-world quality improvement project in the regional ICUs of five tertiary care children's hospitals. Participation was limited to acutely ill Medi-Cal beneficiaries who were admitted November 2018 to May 2020, were <1 year old and within one week of hospitalization, or had just developed an abnormal response to therapy. The whole cohort received RPM. There were two prespecified primary outcomes-changes in medical care reported by physicians and changes in the cost of care. The majority of infants were from underserved populations. Of 184 infants enrolled, 74 (40%) received a diagnosis by rWGS that explained their admission in a median time of 3 days. In 58 (32%) affected individuals, rWGS led to changes in medical care. Testing and precision medicine cost 1.7millionandledto1.7 million and led to 1.7millionandledto2.2-2.9 million cost savings. rWGS-based RPM had clinical utility and reduced net health care expenditures for infants in regional ICUs. rWGS should be considered early in ICU admission when the underlying etiology is unclear.
Molecular Genetics and Metabolism, 2019
Low-dose agalsidase beta treatment in male pediatric patients with Fabry disease: A 5-year random... more Low-dose agalsidase beta treatment in male pediatric patients with Fabry disease: A 5-year randomized controlled trial
American Journal of Medical Genetics Part A, 2019
The neurofibromatoses, which include neurofibromatosis type I (NF1), neurofibromatosis type II (N... more The neurofibromatoses, which include neurofibromatosis type I (NF1), neurofibromatosis type II (NF2), and schwannomatosis, are a group of syndromes characterized by tumor growth in the nervous system. The RASopathies are a group of syndromes caused by germline mutations in genes that encode components of the RAS/mitogen‐activated protein kinase (MAPK) pathway. The RASopathies include NF1, Noonan syndrome, Noonan syndrome with multiple lentigines, Costello syndrome, cardio‐facio‐cutaneous syndrome, Legius syndrome, capillary malformation arterio‐venous malformation syndrome, and SYNGAP1 autism. Due to their common underlying pathogenetic etiology, all these syndromes have significant phenotypic overlap of which one common feature include a predisposition to tumors, which may be benign or malignant. Together as a group, they represent one of the most common multiple congenital anomaly syndromes estimating to affect approximately one in 1000 individuals worldwide. The subcontinent of I...
Molecular genetics & genomic medicine, Jan 12, 2018
The p.Asn215Ser or p.N215S GLA variant has been associated with late-onset cardiac variant of Fab... more The p.Asn215Ser or p.N215S GLA variant has been associated with late-onset cardiac variant of Fabry disease. To expand on the scarce phenotype data, we analyzed natural history data from 125 p.N215S patients (66 females, 59 males) enrolled in the Fabry Registry (NCT00196742) and compared it with data from 401 patients (237 females, 164 males) harboring mutations associated with classic Fabry disease. We evaluated interventricular septum thickness (IVST), left ventricular posterior wall thickness (LVPWT), estimated glomerular filtration rate and severe clinical events. In p.N215S males, mildly abnormal mean IVST and LVPWT values were observed in patients aged 25-34 years, and values gradually increased with advancing age. Mean values were similar to those of classic males. In p.N215S females, these abnormalities occurred primarily in patients aged 55-64 years. Severe clinical events in p.N215S patients were mainly cardiac (males 31%, females 8%) while renal and cerebrovascular events...
Molecular Genetics and Metabolism, 2017
Molecular Genetics and Metabolism, 2017