737 results match your criteria Neurogenetics [Journal]


PTCD3 mutations cause Leigh-like rather than Leigh syndrome.

Neurogenetics 2019 Jan 31. Epub 2019 Jan 31.

Disciplina de Neurociência, Escola Paulista de Medicina/Universidade Federal de São Paulo/. (EPM/UNIFESP), São Paulo, Brazil.

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http://link.springer.com/10.1007/s10048-019-00566-5
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http://dx.doi.org/10.1007/s10048-019-00566-5DOI Listing
January 2019
2 Reads

Clinical and molecular studies in two new cases of ARSACS.

Neurogenetics 2019 Jan 24. Epub 2019 Jan 24.

Molecular Medicine, IRCCS Fondazione Stella Maris, via dei Giacinti 2 Calambrone, 56128, Pisa, Italy.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an early-onset neurodevelopmental disorder characterized by the association of spastic ataxia and sensorimotor neuropathy. Additional features include retinal changes and cognitive impairment. Today, next-generation sequencing (NGS) techniques are allowing the rapid identification of a growing number of missense variants, even in less typical forms of the disease, but the pathogenic significance of these changes is often difficult to establish on the basis of classic bioinformatics criteria and genotype/phenotype correlations. Read More

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http://link.springer.com/10.1007/s10048-019-00564-7
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http://dx.doi.org/10.1007/s10048-019-00564-7DOI Listing
January 2019
4 Reads

Oxygen consumption rate for evaluation of COQ2 variants associated with multiple system atrophy.

Neurogenetics 2019 Jan 7. Epub 2019 Jan 7.

Department of Neurology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

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http://dx.doi.org/10.1007/s10048-018-0563-7DOI Listing
January 2019
1 Read

Mitochondrial ribosomal protein PTCD3 mutations cause oxidative phosphorylation defects with Leigh syndrome.

Neurogenetics 2019 Jan 3. Epub 2019 Jan 3.

Diagnostics and Therapeutics of Intractable Diseases, Intractable Disease Research Center, Graduate School of Medicine, Juntendo University, Hongo 2-1-1, Bunkyo-ku, Tokyo, 113-8421, Japan.

Pentatricopeptide repeat domain proteins are a large family of RNA-binding proteins involved in mitochondrial RNA editing, stability, and translation. Mitochondrial translation machinery defects are an expanding group of genetic diseases in humans. We describe a patient who presented with low birth weight, mental retardation, and optic atrophy. Read More

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http://link.springer.com/10.1007/s10048-018-0561-9
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http://dx.doi.org/10.1007/s10048-018-0561-9DOI Listing
January 2019
8 Reads

Sudden unexpected death with rare compound heterozygous variants in PRICKLE1.

Neurogenetics 2018 Dec 18. Epub 2018 Dec 18.

Department of Legal Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.

Progressive myoclonus epilepsy-ataxia syndrome (EPM5) is an autosomal recessive form of progressive myoclonus epilepsy that has been associated with a homozygous missense mutation in PRICKLE1. We report a 23-year-old male who died shortly after refractory convulsion and respiratory failure. Autopsy showed unilateral hippocampal malformation without significant neuronal loss or gliosis. Read More

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http://dx.doi.org/10.1007/s10048-018-0562-8DOI Listing
December 2018
1 Read

Periodontal Ehlers-Danlos syndrome is associated with leukoencephalopathy.

Neurogenetics 2018 Dec 8. Epub 2018 Dec 8.

Department of Child Neurology and Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.

Here, we report brain white matter alterations in individuals clinically and genetically diagnosed with periodontal Ehlers-Danlos syndrome, a rare disease characterized by premature loss of teeth and connective tissue abnormalities. Eight individuals of two families clinically diagnosed with periodontal Ehlers-Danlos syndrome were included in the present study and underwent general physical, dental, and neurological examination. Whole exome sequencing was performed, and all patients included in the study underwent MRI of the brain. Read More

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http://link.springer.com/10.1007/s10048-018-0560-x
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http://dx.doi.org/10.1007/s10048-018-0560-xDOI Listing
December 2018
14 Reads

Novel case of neurodegeneration with brain iron accumulation 4 (NBIA4) caused by a pathogenic variant affecting splicing.

Neurogenetics 2018 Dec 3;19(4):257-260. Epub 2018 Nov 3.

Research Centre for Medical Genetics Moskvorechie 1, Moscow, Russia, 115522.

Neurodegeneration with brain iron accumulation type 4 (NBIA4) also known as MPAN (mitochondria protein-associated neurodegeneration) is a rare neurological disorder which main feature is brain iron accumulation most frequently in the globus pallidus and substantia nigra. Whole exome sequencing (WES) in a 12-year-old patient revealed 2 variants in the C19orf12 gene, a previously reported common 11 bp deletion c.204_214del11, p. Read More

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http://link.springer.com/10.1007/s10048-018-0558-4
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http://dx.doi.org/10.1007/s10048-018-0558-4DOI Listing
December 2018
7 Reads

Ataxia telangiectasia alters the ApoB and reelin pathway.

Neurogenetics 2018 Dec 21;19(4):237-255. Epub 2018 Oct 21.

Division for Neurology, Department for Children and Adolescents, Goethe University, 60590, Frankfurt am Main, Germany.

Autosomal recessive ataxia telangiectasia (A-T) is characterized by radiosensitivity, immunodeficiency, and cerebellar neurodegeneration. A-T is caused by inactivating mutations in the ataxia telangiectasiamutated (ATM) gene, a serine-threonine protein kinase involved in DNA damage response and excitatory neurotransmission. The selective vulnerability of cerebellar Purkinje neurons (PN) to A-T is not well understood. Read More

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http://link.springer.com/10.1007/s10048-018-0557-5
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http://dx.doi.org/10.1007/s10048-018-0557-5DOI Listing
December 2018
25 Reads

Homozygous mutation in MFSD2A, encoding a lysolipid transporter for docosahexanoic acid, is associated with microcephaly and hypomyelination.

Neurogenetics 2018 Dec 24;19(4):227-235. Epub 2018 Jul 24.

Pediatric Neurology Unit, Hadassah-Hebrew University Medical Center, 9112001, Jerusalem, Israel.

The major facilitator superfamily domain-containing protein 2A (MFSD2A) is a constituent of the blood-brain barrier and functions to transport lysophosphatidylcholines (LPCs) into the central nervous system. LPCs such as that derived from docosahexanoic acid (DHA) are indispensable to neurogenesis and maintenance of neurons, yet cannot be synthesized within the brain and are dependent on MFSD2A for brain uptake. Recent studies have implicated MFSD2A mutations in lethal and non-lethal microcephaly syndromes, with the severity correlating to the residual activity of the transporter. Read More

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http://dx.doi.org/10.1007/s10048-018-0556-6DOI Listing
December 2018
10 Reads

The polynucleotide kinase 3'-phosphatase gene (PNKP) is involved in Charcot-Marie-Tooth disease (CMT2B2) previously related to MED25.

Neurogenetics 2018 Dec 24;19(4):215-225. Epub 2018 Jul 24.

Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.

Charcot-Marie-Tooth disease (CMT) represents a heterogeneous group of hereditary peripheral neuropathies. We previously reported a CMT locus on chromosome 19q13.3 segregating with the disease in a large Costa Rican family with axonal neuropathy and autosomal recessive pattern of inheritance (CMT2B2). Read More

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http://dx.doi.org/10.1007/s10048-018-0555-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6280876PMC
December 2018
5 Reads

Correction to: Incidental diagnosis of tuberous sclerosis complex by exome sequencing in three families with subclinical findings.

Neurogenetics 2018 Dec;19(4):261-262

Department of Pathology and Laboratory Medicine, Children's Mercy Hospitals, Kansas City, MO, 64108, USA.

The published online version contain mistake in the author list. Instead of "A.M. Read More

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http://dx.doi.org/10.1007/s10048-018-0554-8DOI Listing
December 2018
1 Read

FUS(1-359) transgenic mice as a model of ALS: pathophysiological and molecular aspects of the proteinopathy.

Neurogenetics 2018 Aug 7;19(3):189-204. Epub 2018 Jul 7.

Institute of Physiologically Active Compounds RAS, Chernogolovka, Russian Federation, 142432.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that leads to the eventual death of motor neurons. Described cases of familial ALS have emphasized the significance of protein misfolding and aggregation of two functionally related proteins, FUS (fused in sarcoma) and TDP-43, implicated in RNA metabolism. Herein, we performed a comprehensive analysis of the in vivo model of FUS-mediated proteinopathy (ΔFUS(1-359) mice). Read More

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http://dx.doi.org/10.1007/s10048-018-0553-9DOI Listing
August 2018
15 Reads

R106C TFG variant causes infantile neuroaxonal dystrophy "plus" syndrome.

Neurogenetics 2018 Aug 3;19(3):179-187. Epub 2018 Jul 3.

Molecular Neurogenetics Unit, IRCCS Foundation, C. Besta Neurological Institute, Via L. Temolo n. 4, 20126, Milan, Italy.

TFG (tropomyosin-receptor kinase fused gene) encodes an essential protein in the regulation of vesicular trafficking between endoplasmic reticulum and Golgi apparatus. The homozygous variant c.316C > T within TFG has been previously associated with a complicated hereditary spastic paraplegia (HSP) phenotype in two unrelated Indian families. Read More

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http://dx.doi.org/10.1007/s10048-018-0552-xDOI Listing
August 2018
12 Reads

Clinical and genetic study of Tunisian families with genetic generalized epilepsy: contribution of CACNA1H and MAST4 genes.

Neurogenetics 2018 Aug 12;19(3):165-178. Epub 2018 Jun 12.

UPMC Univ Paris 06, Inserm, CNRS, APHP, Institut du Cerveau et la Moelle (ICM), Hôpital Pitié-Salpêtrière, Sorbonne Universités, Paris, France.

Genetic generalized epilepsies (GGE) (childhood absence epilepsy (CAE), juvenile myoclonic epilepsy (JME) and epilepsy with generalized tonic-clonic seizures (GTCS)) are mainly determined by genetic factors. Since few mutations were identified in rare families with autosomal dominant GGE, a polygenic inheritance was suspected in most patients. Recent studies on large American or European cohorts of sporadic cases showed that susceptibility genes were numerous although their variants were rare, making their identification difficult. Read More

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http://dx.doi.org/10.1007/s10048-018-0550-zDOI Listing
August 2018
18 Reads

Incidental diagnosis of tuberous sclerosis complex by exome sequencing in three families with subclinical findings.

Neurogenetics 2018 Aug 20;19(3):205-213. Epub 2018 Jun 20.

Department of Pathology and Laboratory Medicine, Children's Mercy Hospitals, Kansas City, MO, 64108, USA.

Tuberous sclerosis complex (TSC) is an autosomal-dominant neurocutaneous disorder characterized by lesions and benign tumors in multiple organ systems including the brain, skin, heart, eyes, kidneys, and lungs. The phenotype is highly variable, although penetrance is reportedly complete. We report the molecular diagnosis of TSC in individuals exhibiting extreme intra-familial variability, including the incidental diagnosis of asymptomatic family members. Read More

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http://dx.doi.org/10.1007/s10048-018-0551-yDOI Listing
August 2018
14 Reads

Whole exome sequencing in Dandy-Walker variant with intellectual disability reveals an activating CIP2A mutation as novel genetic cause.

Neurogenetics 2018 Aug 30;19(3):157-163. Epub 2018 May 30.

Department of Laboratory Medicine, China Medical University Hospital, #2 Yude Road, Taichung, 40447, Taiwan, Republic of China.

Dandy-Walker malformation (DWM) has been reported to have heterogeneous causes, including mutations in genes of fibroblast growth factors and in genes in the sonic hedgehog (Shh) signaling pathway. Here, we identified an activating cancerous inhibitor of protein phosphatase 2A (CIP2A) p.D269V mutation, located at the predicted protein-protein interaction groove, as a novel genetic cause of Dandy-Walker variant (DWV). Read More

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http://dx.doi.org/10.1007/s10048-018-0548-6DOI Listing
August 2018
4 Reads

A novel missense variant in the SDR domain of the WWOX gene leads to complete loss of WWOX protein with early-onset epileptic encephalopathy and severe developmental delay.

Neurogenetics 2018 Aug 28;19(3):151-156. Epub 2018 May 28.

Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

The human WWOX (WW domain-containing oxidoreductase) gene, originally known as a tumor suppressor gene, has been shown to be important for brain function and development. In recent years, mutations in WWOX have been associated with a wide phenotypic spectrum of autosomal recessively inherited neurodevelopmental disorders. Whole exome sequencing was completed followed by Sanger sequencing to verify segregation of the identified variants. Read More

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http://dx.doi.org/10.1007/s10048-018-0549-5DOI Listing
August 2018
1 Read

Compound heterozygous mutations in two different domains of ALDH18A1 do not affect the amino acid levels in a patient with hereditary spastic paraplegia.

Neurogenetics 2018 May 12. Epub 2018 May 12.

Department of Clinical Genetics, Odense University Hospital, J. B. Winsløws Vej 4, 5000, Odense C, Denmark.

Mutations in ALDH18A1 can cause autosomal recessive and dominant hereditary spastic paraplegia and autosomal recessive and dominant cutis laxa. ALDH18A1 encodes delta-1-pyrroline-5-carboxylate synthetase (P5CS), which consists of two domains, the glutamate 5-kinase (G5K) and the gamma-glutamyl phosphate reductase (GR5P) domain. The location of the mutations in the gene has influence on whether the amino acid levels are affected. Read More

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http://link.springer.com/10.1007/s10048-018-0547-7
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http://dx.doi.org/10.1007/s10048-018-0547-7DOI Listing
May 2018
11 Reads

Toward deciphering the mechanistic role of variations in the Rep1 repeat site in the transcription regulation of SNCA gene.

Neurogenetics 2018 Aug 5;19(3):135-144. Epub 2018 May 5.

Center for Genomic and Computational Biology, Duke University Medical Center, Durham, NC, 27710, USA.

Short structural variants-variants other than single nucleotide polymorphisms-are hypothesized to contribute to many complex diseases, possibly by modulating gene expression. However, the molecular mechanisms by which noncoding short structural variants exert their effects on gene regulation have not been discovered. Here, we study simple sequence repeats (SSRs), a common class of short structural variants. Read More

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http://dx.doi.org/10.1007/s10048-018-0546-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6054541PMC

The impact of next-generation sequencing on the diagnosis of pediatric-onset hereditary spastic paraplegias: new genotype-phenotype correlations for rare HSP-related genes.

Neurogenetics 2018 May 24;19(2):111-121. Epub 2018 Apr 24.

Unit of Neuromuscular and Neurodegenerative Disorders, Ospedale Pediatrico Bambino Gesù, Polo di Ricerca S. Paolo, V.le S. Paolo, 15, 00146, Rome, Italy.

Hereditary spastic paraplegias (HSP) are clinical and genetic heterogeneous diseases with more than 80 disease genes identified thus far. Studies on large cohorts of HSP patients showed that, by means of current technologies, the percentage of genetically solved cases is close to 50%. Notably, the percentage of molecularly confirmed diagnoses decreases significantly in sporadic patients. Read More

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http://dx.doi.org/10.1007/s10048-018-0545-9DOI Listing
May 2018
3 Reads
2.880 Impact Factor

Genetic test utilization and diagnostic yield in adult patients with neurological disorders.

Neurogenetics 2018 May 28;19(2):105-110. Epub 2018 Mar 28.

Department of Neurology, University of Pennsylvania, 330 South 9th Street, Second Floor, Philadelphia, PA, 19107, USA.

To determine the diagnostic yield of different genetic test modalities in adult patients with neurological disorders, we evaluated all adult patients seen for genetic diagnostic evaluation in the outpatient neurology practice at the University of Pennsylvania between January 2016 and April 2017 as part of the newly created Penn Neurogenetics Program. Subjects were identified through our electronic medical system as those evaluated by the Program's single clinical genetic counselor in that period. A total of 377 patients were evaluated by the Penn Neurogenetics Program in different settings and genetic testing recommended. Read More

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http://dx.doi.org/10.1007/s10048-018-0544-xDOI Listing
May 2018
5 Reads

In vitro efficacy of ARQ 092, an allosteric AKT inhibitor, on primary fibroblast cells derived from patients with PIK3CA-related overgrowth spectrum (PROS).

Neurogenetics 2018 May 16;19(2):77-91. Epub 2018 Mar 16.

Division of Medical Genetics, Department of Biomedical Sciences and Human Oncology (DIMO), University of Bari "Aldo Moro", Piazza G. Cesare, 11, Bari, Italy.

Postzygotic mutations of the PIK3CA [phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha] gene constitutively activate the PI3K/AKT/mTOR pathway in PIK3CA-related overgrowth spectrum (PROS) patients, causing congenital mosaic tissue overgrowth that even multiple surgeries cannot solve. mTOR inhibitors are empirically tested and given for compassionate use in these patients. PROS patients could be ideal candidates for enrolment in trials with PI3K/AKT pathway inhibitors, considering the "clean" cellular setting in which a unique driver, a PIK3CA mutation, is present. Read More

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http://dx.doi.org/10.1007/s10048-018-0540-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5956072PMC
May 2018
3 Reads

MED13L-related intellectual disability: involvement of missense variants and delineation of the phenotype.

Neurogenetics 2018 May 6;19(2):93-103. Epub 2018 Mar 6.

University of Lille, EA 7364-RADEME, Lille, France.

Molecular anomalies in MED13L, leading to haploinsufficiency, have been reported in patients with moderate to severe intellectual disability (ID) and distinct facial features, with or without congenital heart defects. Phenotype of the patients was referred to "MED13L haploinsufficiency syndrome." Missense variants in MED13L were already previously described to cause the MED13L-related syndrome, but only in a limited number of patients. Read More

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http://link.springer.com/10.1007/s10048-018-0541-0
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http://dx.doi.org/10.1007/s10048-018-0541-0DOI Listing
May 2018
20 Reads

Reply to 'Letter to Editor by Finsterer J and Zarrouk-Mahjoub S: Phenotypic manifestations of the m.8969G>A variant'.

Neurogenetics 2018 May 26;19(2):133-134. Epub 2018 Feb 26.

Research Programs Unit, Molecular Neurology, Biomedicum-Helsinki, University of Helsinki, Helsinki, Finland.

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http://dx.doi.org/10.1007/s10048-018-0542-zDOI Listing
May 2018
28 Reads

Phenotypic manifestations of the m.8969G>A variant.

Neurogenetics 2018 May 26;19(2):131-132. Epub 2018 Feb 26.

Pasteur Institute of Tunis, University of Tunis El Manar and Genomics Platform, Tunis, Tunisia.

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http://dx.doi.org/10.1007/s10048-018-0543-yDOI Listing
May 2018
5 Reads

Clinical and neuroimaging features of autosomal recessive spastic paraplegia 35 (SPG35): case reports, new mutations, and brief literature review.

Neurogenetics 2018 May 8;19(2):123-130. Epub 2018 Feb 8.

IRCCS Stella Maris, via dei Giacinti 2, 56128, Pisa, Calambrone, Italy.

Spastic paraplegia 35 (SPG35) is a recessive condition characterized by childhood onset, progressive course, complicated by dystonia, dysarthria, cognitive impairment, and epilepsy. Mutations in the FA2H gene have been described in several families, leading to the proposal of a single entity, named fatty acid hydrolase-associated neurodegeneration (FAHN). Several reports have described a polymorphic radiological picture with white matter lesions of various degrees and a distinct form of neurodegeneration with brain iron accumulation. Read More

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http://dx.doi.org/10.1007/s10048-018-0538-8DOI Listing
May 2018
22 Reads
2.884 Impact Factor

WES homozygosity mapping in a recessive form of Charcot-Marie-Tooth neuropathy reveals intronic GDAP1 variant leading to a premature stop codon.

Neurogenetics 2018 May 2;19(2):67-76. Epub 2018 Feb 2.

Centre de Référence de pathologie neuromusculaire Paris-Est, Institut de Myologie, GHU Pitié-Salpêtrière, Paris, France.

Charcot-Marie-Tooth disease (CMT) refers to a group of clinically and genetically heterogeneous inherited neuropathies. Ganglioside-induced differentiation-associated protein 1 GDAP1-related CMT has been reported in an autosomal dominant or recessive form in patients presenting either axonal or demyelinating neuropathy. We report two Sri Lankan sisters born to consanguineous parents and presenting with a severe axonal sensorimotor neuropathy. Read More

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http://dx.doi.org/10.1007/s10048-018-0539-7DOI Listing
May 2018
14 Reads

Defective mitochondrial ATPase due to rare mtDNA m.8969G>A mutation-causing lactic acidosis, intellectual disability, and poor growth.

Neurogenetics 2018 Jan 19;19(1):49-53. Epub 2018 Jan 19.

Research Programs Unit, Molecular Neurology, Biomedicum-Helsinki, University of Helsinki, Helsinki, Finland.

Mutations in mitochondrial ATP synthase 6 (MT-ATP6) are a frequent cause of NARP (neurogenic muscle weakness, ataxia, and retinitis pigmentosa) or Leigh syndromes, especially a point mutation at nucleotide position 8993. M.8969G>A is a rare MT-ATP6 mutation, previously reported only in three individuals, causing multisystem disorders with mitochondrial myopathy, lactic acidosis, and sideroblastic anemia or IgA nephropathy. Read More

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http://dx.doi.org/10.1007/s10048-018-0537-9DOI Listing
January 2018
10 Reads

Monogenic disorders that mimic the phenotype of Rett syndrome.

Neurogenetics 2018 Jan 10;19(1):41-47. Epub 2018 Jan 10.

Hugo W. Moser Research Institute at Kennedy Krieger Institute, 707 North Broadway, Baltimore, MD, 21205, USA.

Rett syndrome (RTT) is caused by mutations in methyl-CpG-binding protein 2 (MECP2), but defects in a handful of other genes (e.g., CDKL5, FOXG1, MEF2C) can lead to presentations that resemble, but do not completely mirror, classical RTT. Read More

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http://dx.doi.org/10.1007/s10048-017-0535-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156085PMC
January 2018
5 Reads

The contribution of 7q33 copy number variations for intellectual disability.

Neurogenetics 2018 Jan 19;19(1):27-40. Epub 2017 Dec 19.

Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.

Copy number variations (CNVs) at the 7q33 cytoband are very rarely described in the literature, and almost all of the cases comprise large deletions affecting more than just the q33 segment. We report seven patients (two families with two siblings and their affected mother and one unrelated patient) with neurodevelopmental delay associated with CNVs in 7q33 alone. All the patients presented mild to moderate intellectual disability (ID), dysmorphic features, and a behavioral phenotype characterized by aggressiveness and disinhibition. Read More

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http://dx.doi.org/10.1007/s10048-017-0533-5DOI Listing
January 2018
5 Reads

A novel mutation in LAMC3 associated with generalized polymicrogyria of the cortex and epilepsy.

Neurogenetics 2018 Jan 15;19(1):61-65. Epub 2017 Dec 15.

Division of Neurology, Department of Pediatrics, Children's Hospital of Eastern Ontario, University of Otawa, Ottawa, Ontario, Canada.

Occipital cortical malformation is a rare neurodevelopmental disorder characterized by pachygyria and polymicrogyria of the occipital lobes as well as global developmental delays and seizures. This condition is due to biallelic, loss-of-function mutations in LAMC3 and has been reported in four unrelated families to date. We report an individual with global delays, seizures, and polymicrogyria that extends beyond the occipital lobes and includes the frontal, parietal, temporal, and occipital lobes. Read More

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http://dx.doi.org/10.1007/s10048-017-0534-4DOI Listing
January 2018
6 Reads

Clinical application of next generation sequencing in hereditary spinocerebellar ataxia: increasing the diagnostic yield and broadening the ataxia-spasticity spectrum. A retrospective analysis.

Neurogenetics 2018 Jan 6;19(1):1-8. Epub 2017 Dec 6.

Molecular Medicine, IRCCS Fondazione Stella Maris, via dei Giacinti 2, 56128, Pisa, Italy.

One of the hardest challenges in medical genetics is to reach a molecular diagnosis in the presence of rare brain disorders. Hereditary spinocerebellar ataxia (HA), characterized by high clinical and genetic heterogeneity, is among the diseases that present this challenge. HA can have features overlapping with those of other neurological diseases, especially hereditary spastic paraplegia (HSP), as routine clinical application of next generation sequencing (NGS) has confirmed. Read More

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http://dx.doi.org/10.1007/s10048-017-0532-6DOI Listing
January 2018
4 Reads

First large genomic inversion in familial cerebral cavernous malformation identified by whole genome sequencing.

Neurogenetics 2018 Jan 2;19(1):55-59. Epub 2017 Dec 2.

Department of Human Genetics, University Medicine Greifswald, and Interfaculty Institute of Genetics and Functional Genomics, University of Greifswald, Fleischmannstraße 43, D-17475, Greifswald, Germany.

Familial cerebral cavernous malformations (CCMs) predispose to seizures and hemorrhagic stroke. Molecular genetic analyses of CCM1, CCM2, and CCM3 result in a mutation detection rate of up to 98%. However, only whole genome sequencing (WGS) in combination with the Manta algorithm for analyses of structural variants revealed a heterozygous 24 kB inversion including exon 1 of CCM2 in a 12-year-old boy with familial CCMs. Read More

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http://dx.doi.org/10.1007/s10048-017-0531-7DOI Listing
January 2018
7 Reads

Developing the field of neurogenetics.

Neurogenetics 2017 Dec;18(4):183-184

Department of Neurology, University of California, San Francisco, USA.

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http://dx.doi.org/10.1007/s10048-017-0530-8DOI Listing
December 2017
3 Reads

Identification of rare noncoding sequence variants in gamma-aminobutyric acid A receptor, alpha 4 subunit in autism spectrum disorder.

Neurogenetics 2018 Jan 18;19(1):17-26. Epub 2017 Nov 18.

John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA.

Alterations of the gamma-aminobutyric acid (GABA) signaling system has been strongly linked to the pathophysiology of autism spectrum disorder (ASD). Genetic associations of common variants in GABA receptor subunits, in particular GABRA4 on chromosome 4p12, with ASD have been replicated by several studies. Moreover, molecular investigations have identified altered transcriptional and translational levels of this gene and protein in brains of ASD individuals. Read More

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http://dx.doi.org/10.1007/s10048-017-0529-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5792317PMC
January 2018
31 Reads

ARHGEF9 mutations in epileptic encephalopathy/intellectual disability: toward understanding the mechanism underlying phenotypic variation.

Neurogenetics 2018 Jan 13;19(1):9-16. Epub 2017 Nov 13.

Institute of Neuroscience and Department of Neurology of the Second Affiliated Hospital of Guangzhou Medical University Please check if the affiliations are presented correctly.The affiliations are presented correctly., Chang-Gang-Dong Road 250, Guangzhou, 510260, China.

ARHGEF9 resides on Xq11.1 and encodes collybistin, which is crucial in gephyrin clustering and GABA receptor localization. ARHGEF9 mutations have been identified in patients with heterogeneous phenotypes, including epilepsy of variable severity and intellectual disability. Read More

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http://dx.doi.org/10.1007/s10048-017-0528-2DOI Listing
January 2018
13 Reads

GNE missense mutation in recessive familial amyotrophic lateral sclerosis.

Neurogenetics 2017 Dec 31;18(4):237-243. Epub 2017 Oct 31.

Department of Neurology, School of Medicine, Ankara University, 06230, Ankara, Turkey.

Amyotrophic lateral sclerosis (ALS) is a motor neuron disease eventually leading to death from respiratory failure. Recessive inheritance is very rare. Here, we describe the clinical findings in a consanguineous family with five men afflicted with recessive ALS and the identification of the homozygous mutation responsible for the disorder. Read More

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http://dx.doi.org/10.1007/s10048-017-0527-3DOI Listing
December 2017
5 Reads

Novel GFM2 variants associated with early-onset neurological presentations of mitochondrial disease and impaired expression of OXPHOS subunits.

Neurogenetics 2017 Dec 26;18(4):227-235. Epub 2017 Oct 26.

Wellcome Centre for Mitochondrial Research, Institute of Neuroscience, The Medical School, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.

Mitochondrial diseases are characterised by clinical, molecular and functional heterogeneity, reflecting their bi-genomic control. The nuclear gene GFM2 encodes mtEFG2, a protein with an essential role during the termination stage of mitochondrial translation. We present here two unrelated patients harbouring different and previously unreported compound heterozygous (c. Read More

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http://dx.doi.org/10.1007/s10048-017-0526-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705740PMC
December 2017
27 Reads

Coexistence of CLCN1 and SCN4A mutations in one family suffering from myotonia.

Neurogenetics 2017 Dec 9;18(4):219-225. Epub 2017 Oct 9.

Center for Neuromuscular Diseases and Neuropathies, Unit of Neurology ASST "Spedali Civili", University of Brescia, Brescia, Italy.

Non-dystrophic myotonias are characterized by clinical overlap making it challenging to establish genotype-phenotype correlations. We report clinical and electrophysiological findings in a girl and her father concomitantly harbouring single heterozygous mutations in SCN4A and CLCN1 genes. Functional characterization of N1297S hNav1. Read More

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http://dx.doi.org/10.1007/s10048-017-0525-5DOI Listing
December 2017
12 Reads

A newly distal hereditary motor neuropathy caused by a rare AIFM1 mutation.

Neurogenetics 2017 Dec 3;18(4):245-250. Epub 2017 Oct 3.

Unit of Genetics and Genomics of Neuromuscular and Neurodegenerative Disorders, Centro de Investigación Príncipe Felipe (CIPF), c/ Eduardo Primo Yúfera, 3, 46012, Valencia, Spain.

In two siblings, who suffer from an early childhood-onset axonal polyneuropathy with exclusive involvement of motor fibers, the c.629T>C (p.F210S) mutation was identified in the X-linked AIFM1 gene, which encodes for the apoptosis-inducing factor (AIF). Read More

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http://dx.doi.org/10.1007/s10048-017-0524-6DOI Listing
December 2017
9 Reads

Molecular genetic and clinical characterization of myotonic dystrophy type 1 patients carrying variant repeats within DMPK expansions.

Neurogenetics 2017 Dec 23;18(4):207-218. Epub 2017 Sep 23.

Faculty of Biology, Center for Human Molecular Genetics, University of Belgrade, Studentski trg 16, PO Box 43, Belgrade, 11000, Serbia.

Myotonic dystrophy type 1 (DM1) is caused by a highly unstable expansion of CTG repeats in the DMPK gene. Its huge phenotypic variability cannot be explained solely by the repeat number. Recently, variant repeats within the DMPK expansions have emerged as potential disease modifiers. Read More

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http://dx.doi.org/10.1007/s10048-017-0523-7DOI Listing
December 2017
11 Reads

Molecular diversity of combined and complex dystonia: insights from diagnostic exome sequencing.

Neurogenetics 2017 Dec 28;18(4):195-205. Epub 2017 Aug 28.

Institut für Neurogenomik, Helmholtz Zentrum München, Ingolstädter Landstraße 1, 85764, Neuherberg, Germany.

Combined and complex dystonias are heterogeneous movement disorders combining dystonia with other motor and/or systemic signs. Although we are beginning to understand the diverse molecular causes of these disease entities, clinical pattern recognition and conventional genetic workup achieve an etiological diagnosis only in a minority of cases. Our goal was to provide a window into the variable genetic origins and distinct clinical patterns of combined/complex dystonia more broadly. Read More

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http://dx.doi.org/10.1007/s10048-017-0521-9DOI Listing
December 2017
35 Reads

X-linked hypomyelination with spondylometaphyseal dysplasia (H-SMD) associated with mutations in AIFM1.

Neurogenetics 2017 Dec 26;18(4):185-194. Epub 2017 Aug 26.

Department of Neurology, Children's National Medical Center, Suite 4800, Washington, DC, USA.

An X-linked condition characterized by the combination of hypomyelinating leukodystrophy and spondylometaphyseal dysplasia (H-SMD) has been observed in only four families, with linkage to Xq25-27, and recent genetic characterization in two families with a common AIFM1 mutation. In our study, 12 patients (6 families) with H-SMD were identified and underwent comprehensive assessment accompanied by whole-exome sequencing (WES). Pedigree analysis in all families was consistent with X-linked recessive inheritance. Read More

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http://dx.doi.org/10.1007/s10048-017-0520-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705759PMC
December 2017
20 Reads

Characterization of SNPs in the dopamine-β-hydroxylase gene providing new insights into its structure-function relationship.

Neurogenetics 2017 Jul 13;18(3):155-168. Epub 2017 Jul 13.

Department of Genetics, University of Delhi South Campus, Benito Juarez Road, New Delhi, 110021, India.

Dopamine-β-hydroxylase (DBH, EC 1.14.17. Read More

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http://dx.doi.org/10.1007/s10048-017-0519-3DOI Listing
July 2017
29 Reads

Male patients affected by mosaic PCDH19 mutations: five new cases.

Neurogenetics 2017 Jul 1;18(3):147-153. Epub 2017 Jul 1.

Department of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Lundlaan 6, 3584CG, Utrecht, The Netherlands.

Pathogenic variants in the PCDH19 gene are associated with epilepsy, intellectual disability (ID) and behavioural disturbances. Only heterozygous females and mosaic males are affected, likely due to a disease mechanism named cellular interference. Until now, only four affected mosaic male patients have been described in literature. Read More

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http://dx.doi.org/10.1007/s10048-017-0517-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5522515PMC
July 2017
5 Reads

Rare causes of early-onset dystonia-parkinsonism with cognitive impairment: a de novo PSEN-1 mutation.

Neurogenetics 2017 Jul 29;18(3):175-178. Epub 2017 Jun 29.

Molecular Neurogenetics Unit, IRCCS Foundation C. Besta Neurological Institute, Via L. Temolo n. 4, 20126, Milan, Italy.

Mutations in PSEN1 are responsible for familial Alzheimer's disease (FAD) inherited as autosomal dominant trait, but also de novo mutations have been rarely reported in sporadic early-onset dementia cases. Parkinsonism in FAD has been mainly described in advanced disease stages. We characterized a patient presenting with early-onset dystonia-parkinsonism later complicated by dementia and myoclonus. Read More

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http://dx.doi.org/10.1007/s10048-017-0518-4DOI Listing
July 2017
24 Reads

Severe growth deficiency, microcephaly, intellectual disability, and characteristic facial features are due to a homozygous QARS mutation.

Neurogenetics 2017 Jul 15;18(3):141-146. Epub 2017 Jun 15.

Metabolic-Neurogenetic Clinic, Wolfson Medical Center, Holon, Israel.

Glutaminyl tRNA synthase is highly expressed in the developing fetal human brain. Mutations in the glutaminyl-tRNA synthetase (QARS) gene have been reported in patients with progressive microcephaly, cerebral-cerebellar atrophy, and intractable seizures. We have previously reported a new recessive syndrome of severe linear growth retardation, poor weight gain, microcephaly, characteristic facial features, cutaneous syndactyly of the toes, high myopia, and intellectual disability in two sisters of Ashkenazi-Jewish origin (Eur J Med Genet 2014;57(6):288-92). Read More

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http://dx.doi.org/10.1007/s10048-017-0516-6DOI Listing
July 2017
13 Reads

Hypomyelinating leukodystrophy associated with a deleterious mutation in the ATRN gene.

Neurogenetics 2017 Jul 10;18(3):135-139. Epub 2017 May 10.

Monique and Jacques Roboh Department of Genetic Research, Hadassah, Hebrew University Medical Center, Jerusalem, Israel.

Hypomyelinating leukodystrophies are a group of neurodevelopmental disorders that affect proper formation of the myelin sheath in the central nervous system. They are characterized by developmental delay, hypotonia, spasticity, and variable intellectual disability. We used whole exome analysis to study the molecular basis of hypomyelinating leukodystrophy in two sibs from a consanguineous family. Read More

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http://dx.doi.org/10.1007/s10048-017-0515-7DOI Listing
July 2017
52 Reads

Increased brain expression of GPNMB is associated with genome wide significant risk for Parkinson's disease on chromosome 7p15.3.

Neurogenetics 2017 Jul 8;18(3):121-133. Epub 2017 Apr 8.

Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK.

Genome wide association studies (GWAS) for Parkinson's disease (PD) have previously revealed a significant association with a locus on chromosome 7p15.3, initially designated as the glycoprotein non-metastatic melanoma protein B (GPNMB) locus. In this study, the functional consequences of this association on expression were explored in depth by integrating different expression quantitative trait locus (eQTL) datasets (Braineac, CAGEseq, GTEx, and Phenotype-Genotype Integrator (PheGenI)). Read More

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http://dx.doi.org/10.1007/s10048-017-0514-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5522530PMC
July 2017
37 Reads

Pain insensitivity: distal S6-segment mutations in Na1.9 emerge as critical hotspot.

Neurogenetics 2017 Jul 13;18(3):179-181. Epub 2017 Mar 13.

Autism & Developmental Medicine Institute, Geisinger Health System, Lewisburg, PA, USA.

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http://dx.doi.org/10.1007/s10048-017-0513-9DOI Listing
July 2017
3 Reads