Posts Categorized: Part 28: NEUROGENETICS



Autism-like behaviours in transgenic monkeys overexpressing MeCP2

Posted by & filed under Part 28: NEUROGENETICS.

MECP2 gene is mutated in Rett syndrome and MECP2 duplication is responsible for a severe developmental disorder with autistic phenotypes. A recent work published in Nature reports the generation of MECP2 transgenic monkeys. The transgenic cynomolgus monkeys (Macaca fascicularis) expressing human MeCP2 in the brain exhibit autism-like behaviours and show germline transmission of the transgene. […]



Somatic mutation in single human brain cells

Posted by & filed under Exome sequencing, Part 03: GENERAL THEMES, Part 28: NEUROGENETICS.

Neurons live for decades in a postmitotic state and their genomes are susceptible to DNA damage. Using genome sequencing for individual human brain cells (postmortem), Lodato et al. have searched for somatic single-nucleotide variants (SNVs) in the human brain. After sequencing 36 neurons from the cerebral cortex of three normal individuals, they demonstrated that the […]



MAOA & COMT polymorphisms modifying psychiatric symptoms in Huntington’s

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A cohort of Danish CAG repeat-expansion carriers in HTT gene, diagnosed with Huntington’s disease (HD), was recently published by Vinther-Jensen et al. (2015). This study focused on symptom complexes and searched for modifiers of cognitive impairment and psychiatric symptoms. Based on the results of Vinther-Jensen et al., cognitive impairment and psychiatric symptoms in HD are […]



Variants in SLC6A1 and Doose Syndrome

Posted by & filed under Part 21: MEMBRANE TRANSPORT DISORDERS, Part 28: NEUROGENETICS.

Doose Syndrome, also known as myoclonic-astatic epilepsy, is a form of epilepsy in which the genetic etiology has been somewhat elusive. A recent study by Carvill et al (Am J Hum Genet 2015 May 7;96(5):808-15. doi: 10.1016/j.ajhg.2015.02.016) reports that pathogenic variants in GAT-1, encoded by SLC6A1, can be responsible for up to 4% of cases of myoclonic-astatic epilepsy. Carvill et al. focused on this gene […]



Brain somatic mutations in MTOR cause focal cortical dysplasia and epilepsy

Posted by & filed under Part 28: NEUROGENETICS.

Focal cortical dysplasia type II (FCDII) is a sporadic developmental malformation of the cerebral cortex characterized by dysmorphic neurons, dyslamination and medically refractory epilepsy. Using deep whole-exome sequencing in paired brain-blood DNA from subjects with FCDII, Lim et al. uncovered brain somatic mutations in mechanistic target of rapamycin (MTOR). The identified mutations induced the hyperactivation of […]



Oxytocin restores social behavior in the Cntnap2 mouse model of autism

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Mutations in contactin-associated protein-like 2 (CNTNAP2) cause cortical dysplasia and focal epilepsy syndrome. The knockout of the mouse homolog displays many features of the human disorder. The group of Dr. Geschwind performed an in vivo screen for drugs that improve the abnormal social behavior of Cntnap2 mutant mice and found that acute administration of the neuropeptide oxytocin […]



Genome-wide association study of MMR-related febrile seizures

Posted by & filed under Part 28: NEUROGENETICS.

Feenstra B et al. Common variants associated with general and MMR vaccine-related febrile seizures. Nat Genet. 2014 Dec;46(12):1274-82. Epub 2014 Oct 26. Febrile seizures are a well-known side-effect of MMR (measles-mumps-rubella) vaccination. Polymorphisms associated with an increased risk of febrile seizures in general have been identified previously (particularly in genes encoding ion channels); this study […]



FOXG1 related disorders and outcome

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Patients with FOXG1-related disorders have severe intellectual disability, absent speech, autistic features, and epilepsy. Children with deletions or intragenic mutations of FOXG1 also have postnatal microcephaly and structural corpus callosum abnormalities. Seltzer et al. reported on the epilepsy characteristics and developmental outcome of 30 patients with FOXG1 mutations (23 with deletions or intragenic mutations of FOXG1, and 7 […]



A framework for the interpretation of de novo mutation in human disease

Posted by & filed under Exome sequencing, Part 28: NEUROGENETICS.

Samocha et al. A framework for the interpretation of de novo mutation in human disease. Nat Genet. 2014 Aug 3.   Samocha et al describe a sophisticated statistical model designed to better evaluate data derived from mass exome sequencing studies, specifically with respect to the significance of excesses of de novo mutations in diseases with […]



HMGCR is a genetic modifier for risk, age of onset and MCI conversion to Alzheimer’s disease

Posted by & filed under Part 12: LIPIDS, Part 28: NEUROGENETICS.

Leduc V et al. HMGCR is a genetic modifier for risk, age of onset and MCI conversion to Alzheimer’s disease in a three cohorts study. Mol Psychiatry. 2014 Jul 15 Leduc et al report a new genetic modulator of the risk for sporadic Alzheimer’s disease (AD) occurrence, as well as the risk of conversion from […]