Dennis Lal, PhD
Lerner Research Institute,
9500 Euclid Avenue, Cleveland, Ohio 44195
Phone: (216) 444-6701
Dr. Lal uses genetic data from in-house and globally collected patient cohorts to discover genes related to epilepsy syndromes, to develop novel methods for interpreting missense variants and to characterize patient disease trajectories. Through his research, Dr. Lal hopes to increase our understanding of how alterations in the genome contribute to neurodevelopmental disorders and, ultimately, to improve patient outcomes.
Epilepsy Disease Gene Discovery
Lal D, Reinthaler EM, Schubert J, et al. DEPDC5 mutations in genetic focal epilepsies of childhood. Ann Neurol. 2014 May;75(5):788-92. doi: 10.1002/ana.24127. PMID: 24591017
Lemke JR*, Lal D*, Reinthaler EM, Steiner I, et al. Mutations in GRIN2A cause idiopathic focal epilepsy with rolandic spikes. Nat Genet. 2013 Sep;45(9):1067-72. doi: 10.1038/ng.2728. PMID: 23933819
Reinthaler EM*, Dejanovic B*, Lal D*, et al. Rare variants in γ-aminobutyric acid type A receptor genes in rolandic epilepsy and related syndromes. Ann Neurol.2015 Jun;77(6):972-86. doi: 10.1002/ana.24395 PMID: 25726841
Epilepsy Copy Number Risk Allele Discovery
Dejanovic B*, Lal D*, Catarino CB, et al. Exonic microdeletions of the gephyrin gene impair GABAergic synaptic inhibition in patients with idiopathic generalized epilepsy. Neurobiol Dis. 2014 Jul;67:88-96. doi: 10.1016/j.nbd.2014.02.001. PMID: 24561070
Lal D, Ruppert AK, Trucks H, et al. Burden analysis of rare microdeletions suggests a strong impact of neurodevelopmental genes in genetic generalised epilepsies. PLoS Genet. 2015 May 7;11(5):e1005226. doi: 10.1371/journal.pgen.1005226. PMID: 25950944
Pérez-Palma E, Helbig I, Klein KM, … , Perucca E, Zara F, Weber YG, Lal D. Heterogeneous Contribution of Microdeletions in the Development of Common Generalized and Focal epilepsies. J Med Genet. 2017 Jul 29. pii: jmedgenet-2016-104495. doi: 10.1136/jmedgenet-2016-104495. PubMed PMID: 28756411
Reinthaler EM*, Lal D*, Lebon S, et al. 16p11.2 600 kb Duplications confer risk for typical and atypical Rolandic epilepsy. Hum Mol Genet. 2014 Nov 15;23(22):6069-80. doi: 10.1093/hmg/ddu306. PMID: 24939913
Genetics of Neurodevelopmental Disorders
Hardies K, de Kovel CG, Weckhuysen S, … , Lal D, et al. Recessive mutations in SLC13A5 result in a loss of citrate transport and cause neonatal epilepsy, developmental delay and teeth hypoplasia. Brain. 2015 Nov;138(Pt 11):3238-50. doi: 10.1093/brain/awv263. PMID: 26384929
Lal D, Becker K, Motameny S, et al. Homozygous missense mutation of NDUFV1 as the cause of infantile bilateral striatal necrosis. Neurogenetics. 2013 Feb;14(1):85-7. doi: 10.1007/s10048-013-0355-z. PMID: 23334465
Lal D, Neubauer BA, Toliat MR, et al. Increased Probability of Co-Occurrence of Two Rare Diseases in Consanguineous Families and Resolution of a Complex Phenotype by Next Generation Sequencing. PLoS One. 2016 Jan 20;11(1):e0146040. doi: 10.1371/journal.pone.0146040 PMID: 26789268
Interpretation and Translation of Genetic Variants
Lal D, May P, Samocha K, et al. Gene family information facilitates variant interpretation and identification of disease-associated genes. BioRxiv 2017; doi: https://doi.org/10.1101/159780
Lal D, Reinthaler EM, Dejanovic B, et al. Evaluation of Presumably Disease Causing SCN1A Variants in a Cohort of Common Epilepsy Syndromes. PLoS One. 2016 Mar 18;11(3):e0150426. doi: 10.1371/journal.pone.0150426. PubMed PMID: 26990884
Lemke JR, Geider K, Helbig KL, … , Lal D, et al. Delineating the GRIN1 phenotypic spectrum: A distinct genetic NMDA receptor encephalopathy. Neurology. 2016 Jun 7;86(23):2171-8. doi: 10.1212/WNL.0000000000002740. PMID: 27164704; PubMed Central PMCID: PMC4898312
Neupert LM, Nothnagel M, May P, Palotie A, Daly M, Nürnberg P, Blümcke I, Lal D. Reassessment of Lesion-Associated Gene and Variant Pathogenicity in Focal Human Epilepsies. BioRxiv 2017; doi: https://doi.org/10.1101/130203
Dennis Lal, PhD, Genomic Medicine Institute, received a five-year, $3.3 million award from the National Institutes of Health to study the genetics of focal cortical dysplasia (FCD), one of the most common causes of drug-resistant epilepsy.
An international team of researchers led by Lerner Research Institute has performed for the first time a wide-scale characterization of missense variants from 1,330 disease-associated genes. Published in Proceedings of the National Academy of Sciences, the study identifies features associated with pathogenic and benign variants that reveal the effects of the mutations at a molecular level.
A Cleveland Clinic-led team of researchers has estimated for the first time the frequency of more than 100 rare and severe neurodevelopmental disorders, according to a new study published in Brain. Accurate estimates of disease burden—which were previously unavailable for nearly all of the disorders on this list—are critically important for clinicians, researchers, patient advocacy groups, pharmaceutical companies and policymakers as they make strategic decisions around care and investment priorities.
An international team of researchers led by Cleveland Clinic has developed new genetic-based epilepsy risk scores which may lay the foundation for a more personalized method of epilepsy diagnosis and treatment. This analysis is the largest study of epilepsy genetics to date, as well as the largest study of epilepsy using human samples.
Charis Eng, MD, PhD, Dennis Lal, PhD, and Harry (Adrian) Lesmana, MD, were recently named recipients of VelaSano research awards. VeloSano is Cleveland Clinic’s flagship cancer research fundraising initiative, which has raised more than $24 million since its inaugural year in 2014. Drs. Eng, Lal and Lesmana will receive $125,000 over two years for their projects.