748 results match your criteria Neurogenetics [Journal]


Linkage analysis and whole exome sequencing reveals AHNAK2 as a novel genetic cause for autosomal recessive CMT in a Malaysian family.

Neurogenetics 2019 Apr 22. Epub 2019 Apr 22.

Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia.

Charcot-Marie-Tooth (CMT) disease is a form of inherited peripheral neuropathy that affects motor and sensory neurons. To identify the causative gene in a consanguineous family with autosomal recessive CMT (AR-CMT), we employed a combination of linkage analysis and whole exome sequencing. After excluding known AR-CMT genes, genome-wide linkage analysis mapped the disease locus to a 7. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10048-019-00576-3DOI Listing

Overlap of polymicrogyria, hydrocephalus, and Joubert syndrome in a family with novel truncating mutations in ADGRG1/GPR56 and KIAA0556.

Neurogenetics 2019 May 13;20(2):91-98. Epub 2019 Apr 13.

Institute for Neuroscience, Department of Pharmacology and Physiology, The George Washington University School of Medicine and Health Sciences, Washington, 20037, DC, USA.

Genetic mutations associated with brain malformations can lead to a spectrum of severity and it is often difficult to determine whether there are additional pathogenic variants contributing to the phenotype. Here, we present a family affected by a severe brain malformation including bilateral polymicrogyria, hydrocephalus, patchy white matter signal changes, and cerebellar and pontine hypoplasia with elongated cerebellar peduncles leading to the molar tooth sign. While the malformation is reminiscent of bilateral frontoparietal polymicrogyria (BFPP), the phenotype is more severe than previously reported and also includes features of Joubert syndrome (JBTS). Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10048-019-00577-2DOI Listing
May 2019
2.884 Impact Factor

Truncating biallelic variant in DNAJA1, encoding the co-chaperone Hsp40, is associated with intellectual disability and seizures.

Neurogenetics 2019 May 10;20(2):109-115. Epub 2019 Apr 10.

King Abdullah International Medical Research Center (KAIMRC), College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.

Intellectual disability poses a huge burden on the health care system, and it is one of the most common referral reasons to the genetic and child neurology clinic. Intellectual disability (ID) is genetically heterogeneous, and it is associated with several other neurological conditions. Exome sequencing is a robust genetic tool and has revolutionized the process of molecular diagnosis and novel gene discovery. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10048-019-00573-6DOI Listing
May 2019
1 Read
2.884 Impact Factor

Pathogenic variants in AIMP1 cause pontocerebellar hypoplasia.

Neurogenetics 2019 May 28;20(2):103-108. Epub 2019 Mar 28.

Departments of Pediatrics, Neurology & Neurosurgery, MUHC-Research Institute, McGill University, 1001 Blvd Décarie, Montreal, H4A 3J1, Canada.

Aminoacyl-tRNA synthetase-interacting multifunctional protein 1 (AIMP1) is a non-catalytic component of the multi-tRNA synthetase complex which catalyzes the ligation of amino acids to the correct tRNAs. Pathogenic variants in several aminoacyl-tRNA synthetases genes have been linked to various neurological disorders, including leukodystrophies and pontocerebellar hypoplasias (PCH). To date, loss-of-function variants in AIMP1 have been associated with hypomyelinating leukodystrophy-3 (MIM 260600). Read More

View Article

Download full-text PDF

Source
http://link.springer.com/10.1007/s10048-019-00572-7
Publisher Site
http://dx.doi.org/10.1007/s10048-019-00572-7DOI Listing
May 2019
2 Reads

Rs10230207 genotype confers changes in HDAC9 and TWIST1, but not FERD3L in lymphoblasts from patients with intracranial aneurysm.

Neurogenetics 2019 May 27;20(2):83-89. Epub 2019 Mar 27.

Department of Pharmacology and Toxicology, Michigan State University, Life Sciences B340, 1355 Bogue St., East Lansing, MI, 48824, USA.

Intracranial aneurysms (IA) are weakened outpouchings of the arterial wall in the cerebrovasculature. Rupture of an IA often leads to devastating consequences. The early identification of IA patients is crucial for management of their condition. Read More

View Article

Download full-text PDF

Source
http://link.springer.com/10.1007/s10048-019-00569-2
Publisher Site
http://dx.doi.org/10.1007/s10048-019-00569-2DOI Listing
May 2019
6 Reads

Facioscapulohumeral muscular dystrophy (FSHD) molecular diagnosis: from traditional technology to the NGS era.

Neurogenetics 2019 May 25;20(2):57-64. Epub 2019 Mar 25.

Molecular Genetics Laboratory UILDM, Santa Lucia Foundation, via Ardeatina 354, 00142, Rome, Italy.

Facioscapulohumeral muscular dystrophy (FSHD) is a genetic neuromuscular disorder which mainly affects the muscles of the face, shoulder, and upper arms. FSHD is generally associated with the contraction of D4Z4 macrosatellite repeats on 4q35 chromosome or mutations in SMCHD1, which are responsible of the toxic expression of DUX4 in muscle tissue. Despite the recent application of NGS techniques in the clinical practice, the molecular diagnosis of FSHD is still performed with dated techniques such as Southern blotting. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10048-019-00575-4DOI Listing

Celia's encephalopathy and c.974dupG in BSCL2 gene: a hidden change in a known variant.

Neurogenetics 2019 May 23;20(2):73-82. Epub 2019 Mar 23.

Thyroid and Metabolic Diseases Unit, Biomedical Research Institute (CIMUS)-IDIS, School of Medicine, Universidade de Santiago de Compostela, Santiago, Spain.

Celia's encephalopathy (progressive encephalopathy with/without lipodystrophy (PELD)) is a childhood neurodegenerative disorder with a fatal prognosis before the age of 10, due to the variant c.985C>T in the BSCL2 gene that causes a cryptic splicing site leading to skipping of exon 7. For years, different authors have reported cases of congenital generalized lipodystrophy due to the variant c. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10048-019-00574-5DOI Listing
May 2019
4 Reads

Primary familial brain calcification caused by a novel homozygous MYORG mutation in a consanguineous Italian family.

Neurogenetics 2019 May 21;20(2):99-102. Epub 2019 Mar 21.

Department of Psychiatry, David Geffen School of Medicine, University of California Los Angeles, 695 Charles E. Young Drive South, #3506C Gonda Neuroscience and Genetics Research Center, Los Angeles, CA, 90095, USA.

Primary familial brain calcification (PFBC) is a rare disorder mostly characterized by calcium deposits in the basal ganglia and a wide spectrum of neurologic and psychiatric symptoms, typically inherited as an autosomal dominant trait. Recently, MYORG was reported as the first autosomal recessive causal gene in PFBC patients of Chinese and Middle Eastern origin. Herein, we describe the first PFBC patient of European descent found to carry a novel homozygous MYORG mutation (p. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10048-019-00571-8DOI Listing

Association of ATXN2 intermediate-length CAG repeats with amyotrophic lateral sclerosis correlates with the distributions of normal CAG repeat alleles among individual ethnic populations.

Neurogenetics 2019 May 7;20(2):65-71. Epub 2019 Mar 7.

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

Intermediate-length CAG repeats in ATXN2 have been widely shown to be a risk factor for sporadic amyotrophic lateral sclerosis (SALS). To evaluate the association of ATXN2 intermediate-length CAG repeat alleles with an increased risk of SALS, we investigated distributions of CAG repeat alleles in 394 patients with SALS and 490 control individuals in the Japanese population. In the intermediate-length repeat units of 29 or more, we identified one SALS patient with 31 repeat units and two control individuals with 30 repeat units. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10048-019-00570-9DOI Listing
May 2019
1 Read

Reply to the "Letter to the Editor" from Dr. J Finsterer and colleagues.

Neurogenetics 2019 Mar 21;20(1):55-56. Epub 2019 Feb 21.

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.

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10048-019-00567-4DOI Listing

Next-generation sequencing study reveals the broader variant spectrum of hereditary spastic paraplegia and related phenotypes.

Neurogenetics 2019 Mar 19;20(1):27-38. Epub 2019 Feb 19.

Department of Genetics, Institute of Psychiatry and Neurology, Sobieskiego 9 Street, 02-957, Warsaw, Poland.

Hereditary spastic paraplegias (HSPs) are clinically and genetically heterogeneous neurodegenerative disorders. Numerous genes linked to HSPs, overlapping phenotypes between HSP subtypes and other neurodegenerative disorders and the HSPs' dual mode of inheritance (both dominant and recessive) make the genetic diagnosis of HSPs complex and difficult. Out of the original HSP cohort comprising 306 index cases (familial and isolated) who had been tested according to "traditional workflow/guidelines" by Multiplex Ligation-dependent Probe Amplification (MLPA) and Sanger sequencing, 30 unrelated patients (all familial cases) with unsolved genetic diagnoses were tested using next-generation sequencing (NGS). Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10048-019-00565-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6411833PMC
March 2019
2 Reads

PTCD3 mutations cause Leigh-like rather than Leigh syndrome.

Neurogenetics 2019 Mar 31;20(1):53-54. Epub 2019 Jan 31.

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

View Article

Download full-text PDF

Source
http://link.springer.com/10.1007/s10048-019-00566-5
Publisher Site
http://dx.doi.org/10.1007/s10048-019-00566-5DOI Listing
March 2019
8 Reads

Clinical and molecular studies in two new cases of ARSACS.

Neurogenetics 2019 Mar 24;20(1):45-49. 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

View Article

Download full-text PDF

Source
http://link.springer.com/10.1007/s10048-019-00564-7
Publisher Site
http://dx.doi.org/10.1007/s10048-019-00564-7DOI Listing
March 2019
12 Reads

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

Neurogenetics 2019 Mar 7;20(1):51-52. 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.

View Article

Download full-text PDF

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

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

Neurogenetics 2019 Mar 3;20(1):9-25. 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

View Article

Download full-text PDF

Source
http://link.springer.com/10.1007/s10048-018-0561-9
Publisher Site
http://dx.doi.org/10.1007/s10048-018-0561-9DOI Listing
March 2019
13 Reads

Sudden unexpected death with rare compound heterozygous variants in PRICKLE1.

Neurogenetics 2019 Mar 18;20(1):39-43. 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

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10048-018-0562-8DOI Listing
March 2019
1 Read

Periodontal Ehlers-Danlos syndrome is associated with leukoencephalopathy.

Neurogenetics 2019 Mar 8;20(1):1-8. 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

View Article

Download full-text PDF

Source
http://link.springer.com/10.1007/s10048-018-0560-x
Publisher Site
http://dx.doi.org/10.1007/s10048-018-0560-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6411670PMC
March 2019
23 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

View Article

Download full-text PDF

Source
http://link.springer.com/10.1007/s10048-018-0558-4
Publisher Site
http://dx.doi.org/10.1007/s10048-018-0558-4DOI Listing
December 2018
11 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

View Article

Download full-text PDF

Source
http://link.springer.com/10.1007/s10048-018-0557-5
Publisher Site
http://dx.doi.org/10.1007/s10048-018-0557-5DOI Listing
December 2018
34 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

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10048-018-0556-6DOI Listing
December 2018
12 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

View Article

Download full-text PDF

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

View Article

Download full-text PDF

Source
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

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10048-018-0553-9DOI Listing
August 2018
17 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

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10048-018-0552-xDOI Listing
August 2018
15 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

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10048-018-0550-zDOI Listing
August 2018
24 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

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10048-018-0551-yDOI Listing
August 2018
23 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

View Article

Download full-text PDF

Source
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

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10048-018-0549-5DOI Listing
August 2018
3 Reads

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 Aug 12;19(3):145-149. 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

View Article

Download full-text PDF

Source
http://link.springer.com/10.1007/s10048-018-0547-7
Publisher Site
http://dx.doi.org/10.1007/s10048-018-0547-7DOI Listing
August 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

View Article

Download full-text PDF

Source
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

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10048-018-0545-9DOI Listing
May 2018
9 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

View Article

Download full-text PDF

Source
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

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10048-018-0540-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5956072PMC
May 2018
4 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

View Article

Download full-text PDF

Source
http://link.springer.com/10.1007/s10048-018-0541-0
Publisher Site
http://dx.doi.org/10.1007/s10048-018-0541-0DOI Listing
May 2018
22 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.

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10048-018-0542-zDOI Listing
May 2018
34 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.

View Article

Download full-text PDF

Source
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

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10048-018-0538-8DOI Listing
May 2018
24 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

View Article

Download full-text PDF

Source
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

View Article

Download full-text PDF

Source
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

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10048-017-0535-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156085PMC
January 2018
7 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

View Article

Download full-text PDF

Source
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

View Article

Download full-text PDF

Source
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

View Article

Download full-text PDF

Source
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

View Article

Download full-text PDF

Source
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.

View Article

Download full-text PDF

Source
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

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10048-017-0529-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5792317PMC
January 2018
38 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

View Article

Download full-text PDF

Source
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

View Article

Download full-text PDF

Source
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

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10048-017-0526-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705740PMC
December 2017
28 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

View Article

Download full-text PDF

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