Posts Categorized: Part 28: NEUROGENETICS



Exome sequencing redefining phenotypes

Posted by & filed under Exome sequencing, Part 06: DIAGNOSTIC APPROACHES, Part 28: NEUROGENETICS, Part 30: MULTISYSTEM INBORN ERRORS OF DEVELOPMENT.

One would intuitively expect that Whole-exome sequencing (WES) will help broaden the phenotypic spectrum of known syndromes since in the past only patients closely matching the described phenotype of a documented genetic syndrome would be tested for the respective diagnosis. Some recent examples illustrating the direction the field is moving include the publications of Dr. […]



Pyridoxine responsiveness in PNPO deficiency

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

Plecko B, Paul K, Mills P, et al. (2014) Pyridoxine responsiveness in novel mutations of the PNPO gene. Neurology 82(16): 1425-1433. Pyridoxal 5’-phosphate dependent epilepsy due to pyridox(am)ine 5’-phosphate oxidase deficiency is a newly discovered treatable cause of neonatal epileptic encephalopathy, clinically resembling pyridoxine-dependent epilepsy due to antiquitin deficiency  (Mills, Surtees et al. 2005). PNPO […]



TDP2 protects transcription from abortive topoisomerase activity and is required for normal neural function.

Posted by & filed under Part 28: NEUROGENETICS.

Gomez-Herreros et al. TDP2 protects transcription from abortive topoisomerase activity and is required for normal neural function. Nat Genet. 2014 May;46(5):516-21. doi: 10.1038/ng.2929. Epub 2014 Mar 23. Gomez-Herreros et al identify homozygous mutations in TDP2 as a new cause of intellectual disability, by performing homozygosity mapping and exome sequencing in a consanguineous Irish family with […]



De novo mutations in HCN1 cause early infantile epileptic encephalopathy

Posted by & filed under Part 28: NEUROGENETICS.

Nava C. et al. De novo mutations in HCN1 cause early infantile epileptic encephalopathy. Nat Genet. 2014 Apr 20. doi: 10.1038/ng.2952. [Epub ahead of print] Nava et al identify de novo heterozygous mutations in HCN1 as a new cause of  Dravet-like early infantile epileptic encephalopathy; the group used exome sequencing in parent-offspring trios with fever-sensitive, […]



Maternally inherited mutations in CADPS2: a novel cause for intellectual disability and autism spectrum disorders

Posted by & filed under Part 28: NEUROGENETICS.

Part 28: Neurogenetics Bonora and colleagues have recently identified an intragenic deletion of maternal origin in two siblings with intellectual disability (ID) and epilepsy in the CADPS2 gene, encoding for a synaptic protein involved in neurotrophin release and interaction with dopamine receptor type 2 (D2DR). They next screened 223 additional patients with ID and autism spectrum disorder and identified a […]



Mutation in DMD as a cause of non-specific X-linked intellectual disability without overt muscular dystrophy

Posted by & filed under Part 25: MUSCLE, Part 28: NEUROGENETICS, _.

de Brouwer et al. A 3-base pair deletion, c.9711_9713del, in DMD results in intellectual disability without muscular dystrophy. European Journal of Human Genetics (2014) 22, 480–485.   A very interesting observation, underlining the importance of dystrophin isoforms for the understanding of genotype-phenotype correlations in DMD-associated disorders. The authors describe a family with non-specific X-linked intellectual disability and no clinically observable […]



Neonatal seizures

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Neonatal seizures: Aetiology by means of a standardized work-up. Loman et al. Eur J Paediatr Neurol. 2014 Feb 17. PMID: 24630570 This study explored the incidence of different aetiologies of neonatal seizures in a real cohort of patients. All full-term born neonates from January 2002 till September 2009 with neonatal seizures, admitted to the local neonatal ICU were […]



VPS53 mutations cause progressive cerebello-cerebral atrophy type 2

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

Feinstein M et al. VPS53 mutations cause progressive cerebello-cerebral atrophy type 2. J Med Genet. 2014 Feb 27. doi: 10.1136/jmedgenet-2013-101823. [Epub ahead of print] Progressive cerebello-cerebral atrophy (PCCA), first described in 2003 in six Sephardi Jewish families, is a devastating autosomal recessive neurodegenerative condition presenting in childhood with psychomotor regression, acquired microcephaly, spastic quadriplegia and epilepsy. Neuroimaging […]



ADNP mutations cause autism syndrome

Posted by & filed under Part 28: NEUROGENETICS.

Genetic diagnosis of autism spectrum disorders (ASD) can be established in only a minority of patients. Known genetic causes include copy number variants and monogenic defects, such as Rett and fragile-X syndromes. The genetic heterogeneity within ASD is striking, with even the most frequent causes responsible for only 1% of cases at the most. The large […]



Mutations in CoA Synthase as a cause of NBIA

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Dusi et al (AJHG, 94, 11-22) report mutations in CoA synthase as a cause of neurodegeneration with brain iron accumulation (NBIA). This gene is particularly interesting, as another member of the CoA biosynthetic pathway, PANK2, also causes NBIA. It is not clear why a gene with such seemingly ubiquitous function should cause such specific neurologic […]