In the Literature, cont.
Influence of Polygenic Risk Scores on the Association Between Infections and Schizophrenia
Michael E. Benros et al.
Several studies have suggested an important role of infections in the etiology of schizophrenia; however, shared genetic liability toward infections and schizophrenia could influence the association. This study investigated the possible effect of polygenic risk scores (PRSs) for schizophrenia on the association between infections and the risk of schizophrenia. It found that PRS and a history of infections have independent effects on the risk for schizophrenia, and the common genetic risk measured by PRS did not account for the association with infection in this sample.
GRIN2D Recurrent De Novo Dominant Mutation Causes a Severe Epileptic Encephalopathy Treatable with NMDA Receptor Channel Blockers
Dong Li et al.
Genetic mutations can cause various childhood epilepsy syndromes. In this study, a previously unrecognized missense mutation was found to contribute to seizure activity and resist conventional antiepileptic medications. These results guided a medication change in the treatment of two affected individuals, which resulted in mild to moderate improvement.
Biallelic Mutations in TBCD, Encoding the Tubulin Folding Cofactor D, Perturb Microtubule Dynamics and Cause Early-Onset Encephalopathy
Elisabetta Flex et al.
Microtubules are cytoskeletal elements that support several neuronal processes. This study identified mutations in the TBDC gene, which encodes for proteins necessary for the creation of the structure of microtubules. The defective TBDC gene caused phenotypes akin to neurodevelopmental and neurodegenerative disorders, including developmental delay, intellectual disability, and seizures. The authors suggest that TBCD functioning underlies microtubule production and, in turn, neuronal function and survival in developing brains.
De Novo Mutations in CHD4, an ATP-Dependent Chromatin Remodeler Gene, Cause an Intellectual Disability Syndrome with Distinctive Dysmorphisms
Karin Weiss et al.
Using whole-exome sequencing and web-based gene matching, Weiss et al. identified five individuals with de novo missense substitutions in CHD4, a DNA-binding protein involved in gene transcription, DNA repair, and cell cycle progressions. The individuals exhibit overlapping phenotypes, including developmental delay, intellectual disability, hearing loss, and macrocephaly. The authors suggest that CHD4 contributes to human development and Mendelian disorders driven by chromatin remodeling and modification.
Mutations in MBOAT7, Encoding Lysophosphatidylinositol Acyltransferase I, Lead to Intellectual Disability Accompanied by Epilepsy and Autistic Features
Anide Johansen et al.
The risk of epilepsy among individuals with intellectual disability is approximately ten times that of the general population. This study suggests a role for AA-containing phosphatidylinositols (major lipids in the mammalian brain) in the development of intellectual disability accompanied by epilepsy and autistic features.
NAXE Mutations Disrupt the Cellular NAD(P)HX Repair System and Cause a Lethal Neurometabolic Disorder of Early Childhood
Laura S. Kremer et al.
This study deployed whole-exome sequencing datasets to identify the molecular basis of a disorder of metabolite repair. These findings may be of clinical use during differential diagnosis.
TMEM231 Gene Conversion Associated with Joubert and Meckel-Gruber Syndromes in the Same Family
Dino Maglic et al.
Joubert and Meckel-Gruber syndromes are genetically heterogeneous disorders that share some symptoms and underlying genes. Using whole exome sequencing, Maglic et al. identified the loss of exon 4 in the TMEM231 gene in a family with several children with symptoms of JS and MGS. The authors believe that the spectrum of JS and MGS phenotypes resulted from a gene conversion (which was responsible for the loss of the exon) in combination with missense mutations.
Down-Regulation of SIRT1 Gene Expression in Major Depressive Disorder
Xiong-Jian Luo & Chen Zhang
While major depressive disorder (MDD) is heritable, its genetic underpinnings are largely unknown. The authors of this letter to the editor outline their findings that SIRT1 expression is significantly down-regulated in MDD patients, but note that MDD is most likely also influenced by many yet-undiscovered loci.
The Role of PIEZO2 in Human Mechanosensation
Alexander T. Chesler
This study implicates the stretch-gated ion channel PIEZO2 in mechanosensation, which involves the sense of touch and the ability to detect stimuli related to the body’s relative position and motion.