Johannes R. Lemke
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View article: GRIN2A null variants confer a high risk for early-onset schizophrenia and other mental disorders and potentially enable precision therapy
GRIN2A null variants confer a high risk for early-onset schizophrenia and other mental disorders and potentially enable precision therapy Open
Rare genetic factors have been shown to substantially contribute to mental illness, but so far, no precision treatments for mental disorders have been described. It was recently identified that rare variants in GRIN2A encoding the GluN2A s…
View article: Time flies faster in epilepsy
Time flies faster in epilepsy Open
People with epilepsy have a significantly reduced life expectancy and an increased burden of age-related comorbidities, raising the possibility that epilepsy accelerates biological aging. Seizures trigger molecular and cellular hallmarks o…
View article: The Refined Recurrence Risk of <i>De Novo</i> variants Due to Parental Mosaicism
The Refined Recurrence Risk of <i>De Novo</i> variants Due to Parental Mosaicism Open
Summary Parents of children with genetic disorders due to de novo variants are counselled on a recurrence risk estimate of 1-5% for further affected siblings, while the actual probability varies between 0 and 50%. This discrepancy is well …
View article: Detecting monogenic obesity: a systematic exome-wide workup of over 500 individuals
Detecting monogenic obesity: a systematic exome-wide workup of over 500 individuals Open
Background/objectives Obesity poses a major public health concern. Although BMI heritability is estimated at 40–80%, genetic diagnostics remain challenging. This study aims to (i) assess the diagnostic yield of monogenic obesity in a large…
View article: Assessment of 1863 GRIN2A Variants Contradicts a Role in Tumorigenesis
Assessment of 1863 GRIN2A Variants Contradicts a Role in Tumorigenesis Open
GRIN2A has previously been identified as frequently mutated in tumor samples, leading to a hypothesized involvement of GRIN2A in tumorigenesis. Pathogenic GRIN2A germline variants, on the other hand lead, to neurodevelopmental disorders, w…
View article: De novo variants in<i>KDM2A</i>cause a syndromic neurodevelopmental disorder
De novo variants in<i>KDM2A</i>cause a syndromic neurodevelopmental disorder Open
Germline variants that disrupt components of the epigenetic machinery cause syndromic neurodevelopmental disorders. Using exome and genome sequencing, we identified de novo variants in KDM2A , a lysine demethylase crucial for embryonic dev…
View article: SyMetrics: An Integrated Machine Learning Model for Evaluating the Pathogenicity of Synonymous Variants in the Human Genome
SyMetrics: An Integrated Machine Learning Model for Evaluating the Pathogenicity of Synonymous Variants in the Human Genome Open
Synonymous single nucleotide variants (sSNVs), traditionally seen as neutral, are now recognized for their biological impact. To assess their relevance, we developed SyMetrics, a framework that integrates predictors of splicing, RNA stabil…
View article: Screening for Hypophosphatasia in Adult Patients at a Maximum Care Provider—Retrospective Analyses over Fifteen Years
Screening for Hypophosphatasia in Adult Patients at a Maximum Care Provider—Retrospective Analyses over Fifteen Years Open
Background/Objectives: Hypophosphatasemia (HPE) may be temporary (tHPE) in the context of severe diseases, such as sepsis or trauma, or it may persist (pHPE), indicating an adult form of hypophosphatasia (HPP; OMIM 171760), a rare metaboli…
View article: Exome sequencing in Nigerian children with early‐onset epilepsy syndromes
Exome sequencing in Nigerian children with early‐onset epilepsy syndromes Open
Objective Nigeria, along with other Sub‐Saharan African countries, bears the highest burden of epilepsy worldwide. This high prevalence is attributed to a combination of factors, including a significant incidence of infectious diseases, pe…
View article: Ligand distances as key predictors of pathogenicity and function in NMDA receptors
Ligand distances as key predictors of pathogenicity and function in NMDA receptors Open
Genetic variants in the genes GRIN1, GRIN2A, GRIN2B, and GRIN2D, which encode subunits of the N-methyl-D-aspartate receptor (NMDAR), have been associated with severe and heterogeneous neurologic and neurodevelopmental disorders, including …
View article: Thiamine-Responsive Megaloblastic Anemia Syndrome Mimicking Myelodysplastic Neoplasm
Thiamine-Responsive Megaloblastic Anemia Syndrome Mimicking Myelodysplastic Neoplasm Open
Introduction: Thiamine-responsive megaloblastic anemia syndrome (TRMA) is a rare autosomal recessive disease with a homozygous or compound-heterozygous mutation in the SLC19A2 gene characterized by megaloblastic anemia, diabetes mellitus (…
View article: Screening for Hypophosphatasia in Adult Patients at a Maximum Care Provider – Retrospective Analyses over Fifteen Years
Screening for Hypophosphatasia in Adult Patients at a Maximum Care Provider – Retrospective Analyses over Fifteen Years Open
Introduction: Persistent hypophosphatasia (pHPE) can be an expression of hypophosphatasia (HPP), a rare disorder of bone metabolism resulting from ALPL gene pathogenic variants. The aim of this study was to identify the role of auxiliary g…
View article: Precision Medicine in Angelman Syndrome
Precision Medicine in Angelman Syndrome Open
Angelman syndrome (AS) is a rare neurogenetic disorder caused by a loss of function of UBE3A on the maternal allele. Clinical features include severe neurodevelopmental delay, epilepsy, sleep disturbances, and behavioral disorders. Therapy…
View article: Clinical features and genotype–phenotype correlations in epilepsy patients with de novo <scp><i>DYNC1H1</i></scp> variants
Clinical features and genotype–phenotype correlations in epilepsy patients with de novo <span><i>DYNC1H1</i></span> variants Open
Objective DYNC1H1 variants are involved on a disease spectrum from neuromuscular disorders to neurodevelopmental disorders. DYNC1H1 ‐related epilepsy has been reported in small cohorts. We dissect the electroclinical features of 34 patient…
View article: Genetics and genetic diagnosis of focal childhood epilepsy
Genetics and genetic diagnosis of focal childhood epilepsy Open
Self-limiting focal epilepsies are among the most common forms of epilepsy in children. Based on family studies, a genetic basis is assumed for the epilepsy as well as the typical electroencephalographic (EEG) feature of centrotemporal spi…
View article: Distances from ligands as main predictive features for pathogenicity and functional effect of variants in NMDA receptors
Distances from ligands as main predictive features for pathogenicity and functional effect of variants in NMDA receptors Open
Genetic variants in genes GRIN1 , GRIN2A , GRIN2B , and GRIN2D , which encode subunits of the N-methyl-D-aspartate receptor (NMDAR), have been associated with severe and heterogeneous neurologic diseases. Missense variants in these genes c…
View article: Michael’s missed genetic diagnosis
Michael’s missed genetic diagnosis Open
Michael, after whom the Michael Foundation is named, had been diagnosed with neonatal-onset refractory epilepsy that challenged numerous epileptologists at the time. The seizures disappeared in adolescence but a neurodevelopmental disorder…
View article: Generation of two patient specific GABRD variants and their isogenic controls for modeling epilepsy
Generation of two patient specific GABRD variants and their isogenic controls for modeling epilepsy Open
Developmental and epileptic encephalopathies (DEEs) are early-onset conditions that cause intractable seizures and developmental delays. Missense variants in Gamma-aminobutyric acid type A receptor (GABAAR) subunits commonly cause DEEs. Ah…
View article: Gain-of-function and loss-of-function variants in <i>GRIA3</i> lead to distinct neurodevelopmental phenotypes
Gain-of-function and loss-of-function variants in <i>GRIA3</i> lead to distinct neurodevelopmental phenotypes Open
AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors (AMPARs) mediate fast excitatory neurotransmission in the brain. AMPARs form by homo- or heteromeric assembly of subunits encoded by the GRIA1–GRIA4 genes, of which onl…
View article: Cat eye syndrome: Clinical, cytogenetics and familial findings in a large cohort of 43 patients highlighting the importance of congenital heart disease and inherited cases
Cat eye syndrome: Clinical, cytogenetics and familial findings in a large cohort of 43 patients highlighting the importance of congenital heart disease and inherited cases Open
Cat Eye Syndrome (CES) is a rare genetic disease caused by the presence of a small supernumerary marker chromosome derived from chromosome 22, which results in a partial tetrasomy of 22p‐22q11.21. CES is classically defined by association …
View article: Clinical features, functional consequences, and rescue pharmacology of missense <i>GRID1</i> and <i>GRID2</i> human variants
Clinical features, functional consequences, and rescue pharmacology of missense <i>GRID1</i> and <i>GRID2</i> human variants Open
GRID1 and GRID2 encode the enigmatic GluD1 and GluD2 proteins, which form tetrameric receptors that play important roles in synapse organization and development of the central nervous system. Variation in these genes has been implicated in…
View article: Advanced control strategies for continuous capture of monoclonal antibodies based upon biolayer interferometry
Advanced control strategies for continuous capture of monoclonal antibodies based upon biolayer interferometry Open
The semi and fully continuous production of monoclonal antibodies (mAbs) has been gaining traction as a lower cost, and efficient production of mAbs to broaden patient access. To be truly flexible and adaptive to process demands, the indus…