Network


Latest external collaboration on country level. Dive into details by clicking on the dots.

Hotspot


Dive into the research topics where Janice L. Smith is active.

Publication


Featured researches published by Janice L. Smith.


American Journal of Human Genetics | 2017

De Novo Disruption of the Proteasome Regulatory Subunit PSMD12 Causes a Syndromic Neurodevelopmental Disorder

Sébastien Küry; Thomas Besnard; Frédéric Ebstein; Tahir N. Khan; Tomasz Gambin; Jessica Douglas; Carlos A. Bacino; Stephan J. Sanders; Andrea Lehmann; Xénia Latypova; Kamal Khan; Mathilde Pacault; Stephanie Sacharow; Kimberly Glaser; Eric Bieth; Laurence Perrin-Sabourin; Marie Line Jacquemont; Megan T. Cho; Elizabeth Roeder; Anne Sophie Denommé-Pichon; Kristin G. Monaghan; Bo Yuan; Fan Xia; Sylvain Simon; Dominique Bonneau; Philippe Parent; Brigitte Gilbert-Dussardier; Sylvie Odent; Annick Toutain; Laurent Pasquier

Degradation of proteins by the ubiquitin-proteasome system (UPS) is an essential biological process in the development of eukaryotic organisms. Dysregulation of this mechanism leads to numerous human neurodegenerative or neurodevelopmental disorders. Through a multi-center collaboration, we identified six de novo genomic deletions and four de novo point mutations involving PSMD12, encoding the non-ATPase subunit PSMD12 (aka RPN5) of the 19S regulator of 26S proteasome complex, in unrelated individuals with intellectual disability, congenital malformations, ophthalmologic anomalies, feeding difficulties, deafness, and subtle dysmorphic facial features. We observed reduced PSMD12 levels and an accumulation of ubiquitinated proteins without any impairment of proteasome catalytic activity. Our PSMD12 loss-of-function zebrafish CRISPR/Cas9 model exhibited microcephaly, decreased convolution of the renal tubules, and abnormal craniofacial morphology. Our data support the biological importance of PSMD12 as a scaffolding subunit in proteasome function during development and neurogenesis in particular; they enable the definition of a neurodevelopmental disorder due to PSMD12 variants, expanding the phenotypic spectrum of UPS-dependent disorders.


PLOS Genetics | 2013

Fusion of large-scale genomic knowledge and frequency data computationally prioritizes variants in epilepsy.

Ian M. Campbell; Mitchell Rao; Sean D. Arredondo; Seema R. Lalani; Zhilian Xia; Sung-Hae L. Kang; Weimin Bi; Amy M. Breman; Janice L. Smith; Carlos A. Bacino; Arthur L. Beaudet; Ankita Patel; Sau Wai Cheung; James R. Lupski; Pawel Stankiewicz; Melissa B. Ramocki; Chad A. Shaw

Curation and interpretation of copy number variants identified by genome-wide testing is challenged by the large number of events harbored in each personal genome. Conventional determination of phenotypic relevance relies on patterns of higher frequency in affected individuals versus controls; however, an increasing amount of ascertained variation is rare or private to clans. Consequently, frequency data have less utility to resolve pathogenic from benign. One solution is disease-specific algorithms that leverage gene knowledge together with variant frequency to aid prioritization. We used large-scale resources including Gene Ontology, protein-protein interactions and other annotation systems together with a broad set of 83 genes with known associations to epilepsy to construct a pathogenicity score for the phenotype. We evaluated the score for all annotated human genes and applied Bayesian methods to combine the derived pathogenicity score with frequency information from our diagnostic laboratory. Analysis determined Bayes factors and posterior distributions for each gene. We applied our method to subjects with abnormal chromosomal microarray results and confirmed epilepsy diagnoses gathered by electronic medical record review. Genes deleted in our subjects with epilepsy had significantly higher pathogenicity scores and Bayes factors compared to subjects referred for non-neurologic indications. We also applied our scores to identify a recently validated epilepsy gene in a complex genomic region and to reveal candidate genes for epilepsy. We propose a potential use in clinical decision support for our results in the context of genome-wide screening. Our approach demonstrates the utility of integrative data in medical genomics.


eLife | 2015

NUDT21-spanning CNVs lead to neuropsychiatric disease and altered MeCP2 abundance via alternative polyadenylation

Vincenzo Alessandro Gennarino; Callison E. Alcott; Chun An Chen; Arindam Chaudhury; Madelyn A. Gillentine; Jill A. Rosenfeld; Sumit Parikh; James W. Wheless; Elizabeth Roeder; Dafne D.G. Horovitz; Erin K. Roney; Janice L. Smith; Sau Wai Cheung; Wei Li; Joel R. Neilson; Christian P. Schaaf; Huda Y. Zoghbi

The brain is sensitive to the dose of MeCP2 such that small fluctuations in protein quantity lead to neuropsychiatric disease. Despite the importance of MeCP2 levels to brain function, little is known about its regulation. In this study, we report eleven individuals with neuropsychiatric disease and copy-number variations spanning NUDT21, which encodes a subunit of pre-mRNA cleavage factor Im. Investigations of MECP2 mRNA and protein abundance in patient-derived lymphoblastoid cells from one NUDT21 deletion and three duplication cases show that NUDT21 regulates MeCP2 protein quantity. Elevated NUDT21 increases usage of the distal polyadenylation site in the MECP2 3′ UTR, resulting in an enrichment of inefficiently translated long mRNA isoforms. Furthermore, normalization of NUDT21 via siRNA-mediated knockdown in duplication patient lymphoblasts restores MeCP2 to normal levels. Ultimately, we identify NUDT21 as a novel candidate for intellectual disability and neuropsychiatric disease, and elucidate a mechanism of pathogenesis by MeCP2 dysregulation via altered alternative polyadenylation. DOI: http://dx.doi.org/10.7554/eLife.10782.001


European Journal of Human Genetics | 2015

Neurodevelopmental and neurobehavioral characteristics in males and females with CDKL5 duplications.

Przemyslaw Szafranski; Sailaja Golla; Weihong Jin; Ping Fang; Patricia Hixson; Reuben Matalon; Daniel Kinney; Hans-Georg O. Bock; William J. Craigen; Janice L. Smith; Weimin Bi; Ankita Patel; Sau Wai Cheung; Carlos A. Bacino; Pawel Stankiewicz

Point mutations and genomic deletions of the CDKL5 (STK9) gene on chromosome Xp22 have been reported in patients with severe neurodevelopmental abnormalities, including Rett-like disorders. To date, only larger-sized (8–21 Mb) duplications harboring CDKL5 have been described. We report seven females and four males from seven unrelated families with CDKL5 duplications 540–935 kb in size. Three families of different ethnicities had identical 667kb duplications containing only the shorter CDKL5 isoform. Four affected boys, 8–14 years of age, and three affected girls, 6–8 years of age, manifested autistic behavior, developmental delay, language impairment, and hyperactivity. Of note, two boys and one girl had macrocephaly. Two carrier mothers of the affected boys reported a history of problems with learning and mathematics while at school. None of the patients had epilepsy. Similarly to CDKL5 mutations and deletions, the X-inactivation pattern in all six studied females was random. We hypothesize that the increased dosage of CDKL5 might have affected interactions of this kinase with its substrates, leading to perturbation of synaptic plasticity and learning, and resulting in autistic behavior, developmental and speech delay, hyperactivity, and macrocephaly.


PLOS Genetics | 2016

Mechanisms for Complex Chromosomal Insertions

Shen Gu; Przemyslaw Szafranski; Zeynep Coban Akdemir; Bo Yuan; M.L. Cooper; Maria A. Magriñá; Carlos A. Bacino; Seema R. Lalani; Amy M. Breman; Janice L. Smith; Ankita Patel; Rodger H. Song; Weimin Bi; Sau Wai Cheung; Claudia M.B. Carvalho; Pawel Stankiewicz; James R. Lupski

Chromosomal insertions are genomic rearrangements with a chromosome segment inserted into a non-homologous chromosome or a non-adjacent locus on the same chromosome or the other homologue, constituting ~2% of nonrecurrent copy-number gains. Little is known about the molecular mechanisms of their formation. We identified 16 individuals with complex insertions among 56,000 individuals tested at Baylor Genetics using clinical array comparative genomic hybridization (aCGH) and fluorescence in situ hybridization (FISH). Custom high-density aCGH was performed on 10 individuals with available DNA, and breakpoint junctions were fine-mapped at nucleotide resolution by long-range PCR and DNA sequencing in 6 individuals to glean insights into potential mechanisms of formation. We observed microhomologies and templated insertions at the breakpoint junctions, resembling the breakpoint junction signatures found in complex genomic rearrangements generated by replication-based mechanism(s) with iterative template switches. In addition, we analyzed 5 families with apparently balanced insertion in one parent detected by FISH analysis and found that 3 parents had additional small copy-number variants (CNVs) at one or both sides of the inserting fragments as well as at the inserted sites. We propose that replicative repair can result in interchromosomal complex insertions generated through chromothripsis-like chromoanasynthesis involving two or three chromosomes, and cause a significant fraction of apparently balanced insertions harboring small flanking CNVs.


American Journal of Medical Genetics Part A | 2013

Three cases of isolated terminal deletion of chromosome 8p without heart defects presenting with a mild phenotype.

Rachel D. Burnside; John G. Pappas; Stephanie Sacharow; Carolyn D. Applegate; Ada Hamosh; Inder Gadi; Vikram L. Jaswaney; Elisabeth Keitges; Karen Phillips; Venketaswara R. Potluri; Hiba Risheg; Janice L. Smith; Jim Tepperberg; Stuart Schwartz; Peter Papenhausen

Individuals with isolated terminal deletions of 8p have been well described in the literature, however, molecular characterization, particularly by microarray, of the deletion in most instances is lacking. The phenotype of such individuals falls primarily into two categories: those with cardiac defects, and those without. The architecture of 8p has been demonstrated to contain two inversely oriented segmental duplications at 8p23.1, flanking the gene, GATA4. Haploinsufficiency of this gene has been implicated in cardiac defects seen in numerous individuals with terminal 8p deletion. Current microarray technologies allow for the precise elucidation of the size and gene content of the deleted region. We present three individuals with isolated terminal deletion of 8p distal to the segmental duplication telomeric to GATA4. These individuals present with a relatively mild and nonspecific phenotype including mildly dysmorphic features, developmental delay, speech delay, and early behavior issues.


American Journal of Obstetrics and Gynecology | 2017

Positive predictive value estimates for cell-free noninvasive prenatal screening from data of a large referral genetic diagnostic laboratory

Andrea K. Petersen; Sau Wai Cheung; Janice L. Smith; Weimin Bi; Patricia A. Ward; Sandra Peacock; Alicia Braxton; Ignatia B. Van den Veyver; Amy M. Breman

Background Since its debut in 2011, cell‐free fetal DNA screening has undergone rapid expansion with respect to both utilization and coverage. However, conclusive data regarding the clinical validity and utility of this screening tool, both for the originally included common autosomal and sex‐chromosomal aneuploidies as well as the more recently added chromosomal microdeletion syndromes, have lagged behind. Thus, there is a continued need to educate clinicians and patients about the current benefits and limitations of this screening tool to inform pre‐ and posttest counseling, pre/perinatal decision making, and medical risk assessment/management. Objective The objective of this study was to determine the positive predictive value and false‐positive rates for different chromosomal abnormalities identified by cell‐free fetal DNA screening using a large data set of diagnostic testing results on invasive samples submitted to the laboratory for confirmatory studies. Study Design We tested 712 patient samples sent to our laboratory to confirm a cell‐free fetal DNA screening result, indicating high risk for a chromosome abnormality. We compiled data from all cases in which the indication for confirmatory testing was a positive cell‐free fetal DNA screen, including the common trisomies, sex chromosomal aneuploidies, microdeletion syndromes, and other large genome‐wide copy number abnormalities. Testing modalities included fluorescence in situ hybridization, G‐banded karyotype, and/or chromosomal microarray analysis performed on chorionic villus samples, amniotic fluid, or postnatally obtained blood samples. Positive predictive values and false‐positive rates were calculated from tabulated data. Results The positive predictive values for trisomy 13, 18, and 21 were consistent with previous reports at 45%, 76%, and 84%, respectively. For the microdeletion syndrome regions, positive predictive values ranged from 0% for detection of Cri‐du‐Chat syndrome and Prader‐Willi/Angelman syndrome to 14% for 1p36 deletion syndrome and 21% for 22q11.2 deletion syndrome. Detection of sex chromosomal aneuploidies had positive predictive values of 26% for monosomy X, 50% for 47,XXX, and 86% for 47,XXY. Conclusion The positive predictive values for detection of common autosomal and sex chromosomal aneuploidies by cell‐free fetal DNA screening were comparable with other studies. Identification of microdeletions was associated with lower positive predictive values and higher false‐positive rates, likely because of the low prevalence of the individual targeted microdeletion syndromes in the general population. Although the obtained positive predictive values compare favorably with those seen in traditional screening approaches for common aneuploidies, they highlight the importance of educating clinicians and patients on the limitations of cell‐free fetal DNA screening tests. Improvement of the cell‐free fetal DNA screening technology and continued monitoring of its performance after introduction into clinical practice will be important to fully establish its clinical utility. Nonetheless, our data provide valuable information that may aid result interpretation, patient counseling, and clinical decision making/management.


Prenatal Diagnosis | 2014

Prenatal diagnosis of 5p deletion syndrome in a female fetus leading to identification of the same diagnosis in her mother

Joanne Macayran Nguyen; Candace Gamble; Janice L. Smith; Marianna Raia; Anthony Johnson; Jennifer Czerwinski

Division of Medical Genetics, Department of Pediatrics, University of Texas Health Science Center at Houston, Houston, TX, USA Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston, Houston, TX, USA Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA *Correspondence to: Joanne Nguyen. E-mail: [email protected]


Current Genetic Medicine Reports | 2013

Using Cytogenetic Rearrangements for Cancer Prognosis and Treatment (Pharmacogenetics)

Marilyn Li; April Ewton; Janice L. Smith

Chromosomal rearrangements including translocations, deletions, inversions, and insertions are common genetic alterations in cancer. Over 1,000 recurrent chromosome rearrangements have been reported so far in different human tumors (http://cgap.nci.nih.gov/Chromosomes/Mitelman). Most of these chromosome rearrangements are associated with specific tumor types and bear distinctive diagnostic and prognostic significance. Molecular characterization of these rearrangements has revealed numerous cancer genes, including novel fusion genes, and their normal and aberrant interactions involved in tumorigenesis, and has identified myriad therapeutic targets. With the help of advanced high-throughput technologies, many cryptic chromosome rearrangements undetectable by conventional cytogenetics have recently been discovered and delineated. The understanding of the mechanisms responsible for the formation of recurrent chromosome rearrangements and their biological functions has led to novel treatment regimens that target tumor cells specifically, with minimal impact to normal cells. Here, we review common recurrent chromosome rearrangements in both hematopoietic malignancies and solid tumors, and their clinical significance, with a focus on acquired fusion genes and their therapeutic implications (i.e., pharmacogenetics).


Human Mutation | 2017

Characterization of Chromosomal Abnormalities in Pregnancy Losses Reveals Critical Genes and Loci for Human Early Development

Yiyun Chen; Justin Bartanus; Desheng Liang; Hongmin Zhu; Amy M. Breman; Janice L. Smith; Hua Wang; Zhilin Ren; Ankita Patel; Paweł Stankiewicz; David S. Cram; Sau Wai Cheung; Lingqian Wu; Fuli Yu

Detailed characterization of chromosomal abnormalities, a common cause for congenital abnormalities and pregnancy loss, is critical for elucidating genes for human fetal development. Here, 2,186 product‐of‐conception samples were tested for copy‐number variations (CNVs) at two clinical diagnostic centers using whole‐genome sequencing and high‐resolution chromosomal microarray analysis. We developed a new gene discovery approach to predict potential developmental genes and identified 275 candidate genes from CNVs detected from both datasets. Based on Mouse Genome Informatics (MGI) and Zebrafish model organism database (ZFIN), 75% of identified genes could lead to developmental defects when mutated. Genes involved in embryonic development, gene transcription, and regulation of biological processes were significantly enriched. Especially, transcription factors and gene families sharing specific protein domains predominated, which included known developmental genes such as HOX, NKX homeodomain genes, and helix‐loop‐helix containing HAND2, NEUROG2, and NEUROD1 as well as potential novel developmental genes. We observed that developmental genes were denser in certain chromosomal regions, enabling identification of 31 potential genomic loci with clustered genes associated with development.

Collaboration


Dive into the Janice L. Smith's collaboration.

Top Co-Authors

Avatar

Ankita Patel

Baylor College of Medicine

View shared research outputs
Top Co-Authors

Avatar

Amy M. Breman

Baylor College of Medicine

View shared research outputs
Top Co-Authors

Avatar

Carlos A. Bacino

Baylor College of Medicine

View shared research outputs
Top Co-Authors

Avatar

Bo Yuan

Baylor College of Medicine

View shared research outputs
Top Co-Authors

Avatar

Sau Wai Cheung

Baylor College of Medicine

View shared research outputs
Top Co-Authors

Avatar

Weimin Bi

Baylor College of Medicine

View shared research outputs
Top Co-Authors

Avatar

Tomasz Gambin

Warsaw University of Technology

View shared research outputs
Top Co-Authors

Avatar

Elizabeth Roeder

Baylor College of Medicine

View shared research outputs
Top Co-Authors

Avatar

Jill A. Rosenfeld

Baylor College of Medicine

View shared research outputs
Top Co-Authors

Avatar

Pawel Stankiewicz

Baylor College of Medicine

View shared research outputs
Researchain Logo
Decentralizing Knowledge