Posts Categorized: Part 28: NEUROGENETICS

DOOR syndrome (or DOORS syndrome) genetics

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

In this post, I will describe one of my main research projects, the study of DOOR syndrome, or DOORS syndrome, which stands for : – Deafness (sensorineural) – Onychodystrophy (abnormal nails) – Osteodystrophy (abnormal bones, especially in the digits) – Retardation, mental (now know as intellectual disability) – Seizures The acronym was first used by […]

S-adenosylmethionine and S-adenosyl homocysteine in plasma and cerebrospinal fluid in Rett syndrome and the effect of folinic acid supplementation

Posted by & filed under Part 17: VITAMINS, Part 28: NEUROGENETICS, _.

Hagebeuk EEO et al. S-adenosylmethionine and S-adenosyl homocysteine in plasma and cerebrospinal fluid in Rett syndrome and the effect of folinic acid supplementation. J Inherited Metab Dis (2013) 36:967-972   Rett syndrome, a devastating disorder characterised by neuroregression after an initial period of normalcy, is caused by mutations in the MECP2 gene encoding the methyl […]

SHANK3 overexpression causes manic-like behaviour

Posted by & filed under Part 28: NEUROGENETICS.

Large duplications (and deletions) of the region spanning SHANK3 cause a spectrum of neuropsychiatric disorders. Therefore, SHANK3 dosage is critical for normal brain function. However, SHANK3 overexpression per se has not been established as a cause of human disorders because 22q13 duplications involve several genes. This study reports that Shank3 transgenic mice modelling a human SHANK3 duplication exhibit […]

Do all nerve cells of an individual have the same genome?

Posted by & filed under Part 28: NEUROGENETICS.

As individuals grow older, human neurons appear to diversify (e.g. aneuploid neurons or subchromosomal CNVs in euploid neurons). McConnell et al recently published in Science that mosaic copy number variation (CNV) is abundant in human neurons.   McConnell et al used single-cell genomic approaches to map DNA in neurons obtained from human induced pluripotent stem […]

Mutations in COQ2 in Familial and Sporadic Multiple-System Atrophy

Posted by & filed under Part 10: DISORDERS OF MITOCHONDRIAL FUNCTION, Part 28: NEUROGENETICS, _.

Multiple-system atrophy (MSA) is an adult-onset neurodegenerative disease encompassing various combinations of parkinsonism, autonomic dysfunction, cerebellar ataxia and pyramidal dysfunction. As the neuropathologic diagnosis of MSA requires the finding of cytoplasmic aggregates of alpha-synuclein in oligodendroglia, it is classed among the alpha-synucleinopathies, alongside Parkinson disease and Lewy-body dementia. The disease is generally considered sporadic, though […]

Yunis-Varón syndrome gene identification links this skeletal dysplasia with neurological involvement to phosphoinositide metabolism


Yunis-Varón syndrome is a skeletal dyplasia with features of cleidocranial dysplasia, with digital hypoplasia and severe neurological involvement ( Through exome sequencing, we identified three families with mutations of FIG4, encoding a phosphoinositide phosphatase. This enzyme had previously been implicated in Charcot-Marie-Tooth type 4J (CMT-4J). While CMT-4J is usually caused by a combination of a […]

16p11.2 deletion and autism

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The recurrent ~600 kb 16p11.2 deletion, defined by breakpoints 4 and 5 (BP4-BP5), is among the most frequent known genetic aetiologies of autism spectrum disorder (ASD). Its population prevalence is ~ 1/2000, but in ASD it reaches 1/200. Zufferey et al collected clinical data on 285 deletion carriers and performed detailed evaluations on 72 carriers […]

MTTP allele as a risk factor for metabolic syndrome with atypical antipsychotics

Posted by & filed under Part 28: NEUROGENETICS, Treatment.

Liou et al. recently published a study illustrating that promoter polymorphisms in microsomal triglyceride transfer protein (MTTP) are associated with metabolic syndrome in schizophrenic patients treated with atypical antipsychotics. 456 hospitalized patients with schizophrenia, who had been treated with clozapine (n = 171), olanzapine (n = 91), or risperidone (n = 194) for at least […]

Sturge–Weber Syndrome – GNAQ Somatic Mutation

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The Sturge–Weber syndrome and port-wine stains are caused by a somatic activating mutation in GNAQ. Whole-genome sequencing of DNA from paired samples of visibly affected and normal tissue from 3 persons with the Sturge–Weber syndrome was performed.  A non-synonymous single-nucleotide variant (c.548G?A, p.Arg183Gln) was identified in GNAQ in samples of affected tissue from 88% of […]

New FRMP gene targets: potential for new treatments in FXS/ASD

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Fragile X syndrome (FXS) is typically caused by the loss of fragile X mental retardation 1 (FMR1) expression, which codes for the RNA-binding protein FMRP. Ascano et al. reported the identification of RNA-recognition elements for FMRP, in addition to its target messenger RNAs. Many of FMRP gene targets discovered are involved in brain function and […]