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1.
Heinz Reichmann R. Gold B. Meurers M. Naumann P. Seibel U. Walter T. Klopstock 《Acta neuropathologica》1993,85(6):679-681
Summary We report on the progression of myopathology by comparing two biopsies from a patient with a Kearns-Sayre-Syndrome. The first biopsy was taken in 1979 and showed 10% ragged-red fibers. Myopathic changes were slight including internal nuclei and fiber splitting in 10% of the fibers. Electron microscopy revealed typical mitochondrial abnormalities with regard to number and shape. In 1989 a second biopsy was performed for an extended analysis of mitochondrial DNA. This time less than 5% of all fibers were ragged-red. Severe myopathic changes could be detected which so far has rarely been reported in mitochondrial cytopathy.Supported by the Deutsche Forschungsgemeinschaft (Re 265/6-1 and Re 265/7-1) 相似文献
2.
Stogmann E El Tawil S Wagenstaller J Gaber A Edris S Abdelhady A Assem-Hilger E Leutmezer F Bonelli S Baumgartner C Zimprich F Strom TM Zimprich A 《Neurogenetics》2009,10(1):73-77
Neuronal ceroid lipofuscinoses (NCL) are lysosomal storage disorders and constitute the most common group of progressive neurodegenerative
diseases in childhood. Most NCLs are inherited in a recessive manner and are clinically characterised by a variable age at
onset, epileptic seizures, psychomotor decline, visual impairment and premature death. To date, eight causative genes have
been identified to underlie various clinical forms of NCL. We performed a genome-wide linkage analysis followed by sequencing
the recently described NCL gene MFSD8 in three affected and three unaffected members of a consanguineous Egyptian family with an autosomal recessively inherited
progressive neurodegenerative disorder. The clinical picture of the patients was compatible with a late infantile NCL (LINCL);
however, impairment of the visual system was not a cardinal symptom in the respective family. By linkage analysis, we identified
two putative loci on chromosome 1p36.11-p35.1 and 4q28.1-q28.2. The latter locus (4q28.1-q28.2) contained the MFSD8 gene, comprising a novel homozygous missense mutation in exon 5 (c.362a>g /p.Tyr121Cys), which segregated with the disease
in the three affected sibs. We describe a novel mutation in the previously identified MFSD8 gene in a family with a common phenotype of LINCL, but no clinical report of vision loss. Our results enlarge the mutational
and perhaps the nosological spectrum of one of the recently identified subtypes of NCL, called CLN7.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
3.
Lin YC Murakami T Hayashi YK Nishino I Nonaka I Yuo CY Jong YJ 《Brain & development》2007,29(4):234-238
Limb-girdle muscular dystrophy (LGMD) is a group of hereditary muscle diseases with preferential involvement of the shoulder and pelvic girdle muscles, but with no pathognomonic features as in facioscapulohumeral and congenital muscular dystrophies. We report 18-year-old female with progressive shoulder and pelvic muscle weakness. She had marked restrictive pulmonary dysfunction. Echocardiogram showed mild decrease in ejection fraction of 52% (normal: >55%). She was first seen in our hospital at age 2 years with progressive proximal muscle weakness and elevated creatine kinase (CK) level to 15,290 IU/L, with what clinically and pathologically appeared to be steroid-responsive inflammatory myopathy. She responded dramatically to steroid therapy. Progressive proximal muscle weakness began again at age 8 years. Serum CK was 14,910 IU/L. She was wheelchair-bound by age 12. Muscle biopsy showed dystrophic changes without inflammation with reduced immunoreactivity to an antibody against sugar chain (VIA4-1) of alpha-dystroglycan. On laminin overlay assay, there was a nearly complete loss of laminin-binding activity to alpha-dystroglycan. Genetic analysis of fukutin-related protein (FKRP) gene revealed a novel compound heterozygous mutation of c.823C>T (p.R275C) and c.948delC, confirming the diagnosis of LGMD2I, the first reported case in East Asia. 相似文献
4.
Pelizaeus-Merzbacher disease (PMD) is a rare dysmyelinating disorder due to mutations in the proteolipid protein (PLP) gene. PLP gene mutations are responsible for a broad spectrum of disease, from the most severe form, connatal PMD, to a less severe form, spastic paraplegia 2 (SPG2). We describe here a very mild case of PMD in a patient who presented with nystagmus in early infancy and was unable to walk until 1 year 7 months of age. Brain magnetic resonance imaging (MRI) at 1 year 7 months of age revealed white matter abnormalities typical of PMD. Genetic testing revealed a novel mutation of the PLP gene (Gly197Arg). The patient presented with only mildly ataxic gait and slurred speech at the age of 4 years. Gly197Arg is the first novel mutation located within exon 4 of the PLP gene and associated with mild PMD/SPG2 in a Japanese patient. 相似文献
5.
Lorenzo Peverelli MD Carl A. Gold MD Ali B. Naini PhD Kurenai Tanji MD H. Orhan Akman PhD Michio Hirano MD Salvatore Dimauro MD 《Muscle & nerve》2014,50(2):292-295
Introduction: A 61‐year‐old woman with a 5‐year history of progressive muscle weakness and atrophy had a muscle biopsy characterized by a combination of dystrophic features (necrotic fibers and endomysial fibrosis) and mitochondrial alterations [ragged‐red, cytochrome c oxidase (COX)‐negative fibers]. Methods: Sequencing of the whole mtDNA, assessment of the mutation load in muscle and accessible nonmuscle tissues, and single fiber polymerase chain reaction. Results: Muscle mitochondrial DNA (mtDNA) sequencing revealed a novel heteroplasmic mutation (m.4403G>A) in the gene (MTTM) that encodes tRNAMet. The mutation was not present in accessible nonmuscle tissues from the patient or 2 asymptomatic sisters. Conclusions: The clinical features and muscle morphology in this patient are very similar to those described in a previous patient with a different mutation, also in MTTM, which suggests that mutations in this gene confer a distinctive “dystrophic” quality. This may be a diagnostic clue in patients with isolated mitochondrial myopathy. Muscle Nerve 50:292–295, 2014 相似文献
6.
Golan MP Styczyńska M Jóźwiak K Walecki J Maruszak A Pniewski J Lugiewicz R Filipek S Zekanowski C Barcikowska M 《Experimental neurology》2007,208(2):264-268
A 32-year-old woman diagnosed with very rapidly progressing early-onset Alzheimer's disease (EOAD), age of onset 29 years, and S170F mutation in presenilin 1 gene (PSEN1) is presented. Neuroimaging conducted 2 years after the first symptoms was typical for the advanced stage of Alzheimer's disease (AD), showing cortical brain atrophy, particularly within hippocampus, frontal and temporal cortex. The unaffected parents of the proband are not carriers of the mutation. The paternity was confirmed by microsatellite typing, strongly suggesting de novo origin of S170F mutation. In silico modeling of S170F mutation impact on presenilin 1 (PS1) transmembrane structure indicates that the mutation considerably alters putative interactions of PS1 with other proteins within gamma-secretase complex. 相似文献
7.
Shuichi Izumoto Mami Yamasaki Norio Arita Shoju Hiraga Takanori Ohnishi Ken Fujitani Saburo Sakoda Toru Hayakawa 《Child's nervous system》1996,12(12):742-747
X-linked hydrocephalus is a genetic form of hydrocephalus that frequently occurs in males. It is characterized by ventricular dilatation, mental retardation, deformity of the thumb and spastic paraparesis. Recently, 23 different mutations of the gene for the neural cell adhesion molecule, L1CAM, located at chromosome region Xq28, have been reported, 16 of which were detected in families with X-linked hydrocephalus. We sequenced the coding region of the L1CAM gene of patients from two different families with X-linked hydrocephalus and found a novel mutation at nucleotide residue 1963 in one family. This mutation from adenine to guanine results in an amino acid change from lysine to glutamic acid at residue 655 of the L1CAM protein, which belongs to the fibronectin type III domain. We report another method for the rapid identification of the mutation based on the polymerase chain reaction. This mutation was not detected among 70 X chromosomes from a healthy population. Ours is the first report demonstrating this gene mutation in X-linked hydrocephalus in an Asian population. Our findings further emphasize the evolving genotypic heterogeneity in X-linked hydrocephalus. 相似文献
8.
Robert Laforce Jr. Paul N. Valdmanis Nicolas Dupr Guy A. Rouleau Alexis F. Turgeon Martin Savard 《Clinical neurology and neurosurgery》2009,111(8):691-694
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive disorder characterized by gastrointestinal, extraocular muscle, peripheral nerve, and cerebral white matter involvement. Mutations in the nuclear gene TYMP encoding for thymidine phosphorylase (TP) cause loss of TP activity, systemic accumulation of its substrates in plasma and tissues, as well as alterations in mitochondrial DNA including deletions, depletion, and somatic point mutations. To date, more than 30 mutations have been reported in diverse ethnic populations. We present herein the clinical, neuroimaging, neuromuscular, and molecular findings of the first French Canadian patient with MNGIE caused by a novel homozygous invariant splicing site (IVS5 +1 G>A) mutation of the TYMP gene. 相似文献
9.
Felix Distelmaier Raimund Fahsold Guido Reifenberger Martina Messing-Juenger Jörg Schaper Dominik T. Schneider Ulrich Göbel Ertan Mayatepek Thorsten Rosenbaum 《Child's nervous system》2007,23(3):343-347
Introduction Neurofibromatosis type I (NF1) is one of the most prevalent genetic diseases of the nervous system. Although the majority
of NF1 patients are only mildly affected, the risk of developing malignancies is significantly increased in this population.
Case report Here, we present a 9-year-old girl with clinical stigmata of NF1 and a rapidly evolving glioblastoma multiforme. Molecular
genetic analysis uncovered a novel missense mutation in Exon 32 of the NF1 gene [c.6032C>A(p.Ala2011Glu)].
Discussion The girl’s death 3 days after diagnosis of the brain tumor exemplifies that NF1 still is a life-threatening disease despite
its generally benign course in most patients. However, it remains questionable if a fatal course as reported here can be prevented
by routine MRI screening. 相似文献
10.
V. La Bella M. Liguori R. Cittadella N. Settipani T. Piccoli I. Manna A. Quattrone F. Piccoli 《European journal of neurology》2004,11(8):521-524
We report a novel presenilin 1 (PSN1) mutation (Thr116Ile) in a woman with early onset Alzheimer's disease (AD). This mutation was not found in 100 healthy controls, indicating that this is not a common polymorphism. The patient presented with forgetfulness at age 45, followed over the next 3 years by a worsening of the memory loss and frequent episodes of confusion and spatial disorientation. Neuroimaging studies were consistent with AD. The analysis of the family's pedigree showed that the proband was apparently the only member affected. Because the early death of several close relatives (i.e. the mother and the grandmother) and the demonstration that the father is not a mutation carrier, it is suggested that either a de novo mutation or a censor effect might have occurred. Our finding supports the indication that PSN1 mutations should be searched for in early-onset AD, particularly when a censor effect precludes a precise genetic analysis. 相似文献
11.
Yannick Béjot Guy-Victor Osseby Marie Caillier Thibault Moreau Jean-Louis Laplanche Maurice Giroud 《Clinical neurology and neurosurgery》2010
Genetic transmissible spongiform encephalopathies (TSEs) account for approximately 10–15% of overall human prion diseases worldwide, but genotype–phenotype correlations remain incomplete. Here we report the case of an 80-year-old man who developed rapidly progressive behavioral abnormalities and myoclonus following a stroke. Repeated electroencephalography (EEG) revealed a general slowing of the basic activity, as well as several episodes of triphasic waves, with neither periodic activity nor recorded seizure. 14.3.3 protein was detected in cerebral cerebrospinal fluid, and direct sequencing of the PRNP gene showed an E196K mutation associated with homozygosity for methionine at codon 129. The patient was diagnosed with probable genetic prion disease with a Creutzfeldt-Jakob disease-like phenotype. The PRNP E196K mutation has only rarely been described in the literature, and generally patients exhibited an atypical initial phenotype, mainly involving abnormal behavioral features. Further observations are needed to confirm this particular clinical pattern associated with the mutation. 相似文献
12.
Bitoun M Stojkovic T Prudhon B Maurage CA Latour P Vermersch P Guicheney P 《Neuromuscular disorders : NMD》2008,18(4):334-338
Mutations in dynamin 2 (DNM2) have been associated with autosomal dominant centronuclear myopathy, dominant intermediate Charcot-Marie-Tooth (CMT) type B and CMT2. Here, we report a novel DNM2 mutation in the Pleckstrin homology domain of DNM2 (p.K559del) in a patient with an axonal length-dependent sensorimotor polyneuropathy predominantly affecting the lower limbs. Neuropathy is associated with congenital cataracts, ophthalmoparesis, ptosis and neutropenia. There was no evidence of a skeletal myopathy on EMG or muscle biopsy. We suggest that this constellation of clinical features can help the diagnosis and selection of patients for direct DNM2 genetic analysis. 相似文献
13.
A. Simonati F. Boaretto A. Vettori P. Dabrilli L. Criscuolo N. Rizzuto M. L. Mostacciuolo 《Neurological sciences》2006,27(2):114-117
Abstract A novel missense mutation of the L1CAM gene (Xq28) is described in an adult patient affected with severe mental retardation, spastic paraparesis, adducted thumbs,
agenesis of corpus callosum and microcephaly (L1 disease). We detected a transition c2308G→A in exon 18 that caused an amino
acid change in codon 770. The patient’s mother and two sisters were heterozygous for the same mutation. This newly described
mutation predicts the substitution of an aspartate by asparagine (D770N) in the second fibronectin (Fn2) domain of the extracellular
portion of the mature L1 protein. Even if amino acid substitution does not significantly change the physico-chemical properties
of the Fn2 domain, it seems clear that the integrity of this domain is required to maintain the biological functions of the
protein. The feature peculiar to this patient is the decelerated head growth post-natally, leading to microcephaly. Mutations
of L1CAM associated with prolonged survival may hamper post-natal brain and head growth. 相似文献
14.
Krause S Schlotter-Weigel B Walter MC Najmabadi H Wiendl H Müller-Höcker J Müller-Felber W Pongratz D Lochmüller H 《Neuromuscular disorders : NMD》2003,13(10):830-834
An adult-onset hereditary inclusion body myopathy with sparing of the quadriceps muscle was originally described in Iranian Jews and assigned to a locus on chromosome 9p12–p13. Recently, mutations of the UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE) gene were reported to cause hereditary inclusion body myopathy and one type of distal myopathy in a world-wide distribution. Importantly, the lack of muscle inflammation was used to distinguish hereditary inclusion body myopathy from the sporadic form of inclusion body myopathy. We report a case of a quadriceps-sparing myopathy in a non-Jewish, Iranian patient with a high degree of muscle inflammation. A novel homozygous G-to-A mutation (128933G→A) in exon 7 changing a valine to isoleucine (V367I) in the epimerase domain of the GNE gene was found. We conclude that muscle inflammation is not sufficient to exclude the diagnosis of hereditary inclusion body myopathy. 相似文献
15.
Abdul Qayyum Rana Osama A. Khan Raza Akthar 《Annals of Indian Academy of Neurology》2013,16(2):269-271
Ataxia, although rare, can be a symptom of many debilitating movement disorders. Hereditary ataxias are one subset of this condition and manifest when there is a genetic abnormality involved. Ataxia oculomotor apraxia type 1 (AOA1), an autosomal recessive ataxia, results from a mutation on the aprataxin gene (APTX). We characterized a novel homozygous deletion mutation (IVS4-12delT) on the APTX gene in a 14-year-old male born to consanguineous parents. This case report emphasizes the importance of investigating and increasing awareness of novel genetic mutations in order to help diagnose and further classify hereditary ataxias. 相似文献
16.
17.
Elena D. Markova Pyotr A. Slominsky Sergei N. Illarioshkin Natalya I. Miklina Svetlana N. Popova Svetlana A. Limborska Irina A. Ivanova-Smolenskaya 《European journal of neurology》1999,6(5):605-608
We examined a large family of Ashkenazi Jewish origin with autosomal dominant dopa-responsive dystonia (DRD). Mutation analysis of the GTP cyclohydrolase I gene revealed in affected members a novel point mutation (a C/A change in exon 1) resulting in a threonine-to-lysine substitution at residue 94. The mutation was characterized by variable expressivity and was associated with either a 'classical' DRD phenotype or various atypical phenotypes, such as subtle transitory equinovarus postures of the feet or isolated hand tremor. This observation demonstrates the significance of the molecular testing in establishing the clinical diagnosis of DRD. Copyright Lippincott Williams & Wilkins 相似文献
18.
Mutations in the presenilin-2 (
PS-2
) gene are less frequent than mutations in the
PS-1
gene. All mutations described in the
PS-1
gene were found in early-onset Alzheimer's disease (AD) patients. At present, there are two missense mutations described
for the
PS-2
gene in some AD pedigrees. We have therefore analyzed transmembrane 2 (TM2) and TM5 domains of the
PS-2
gene in AD patients and in a group of age-matched healthy controls. In a patient who was clinically diagnosed as having late-onset
AD, we found a novel missense mutation consisting of a G- 1 A substitution on exon
5
of the
PS-2
gene, which results in a Val to Ile substitution at codon 148 within the predicted TM2 domain of the PS-2 protein. This is
the third mutation described in the
PS-2
gene and the first presenilin mutation detected in a Spanish AD patient. Both, the
N141I
mutation and the
V148I
mutation described here are located within the predicted TM2 domain and both were found in late-onset AD kindreds, whereas
the mutation within the predicted TM5 domain was found in an early-onset AD pedigree. Carriers of mutations within TM2 of
PS-1
have a mean age at onset of 40 years, while the other mutations in
PS-1
occur in families with a mean age at onset of 47 years. In summary, we report here the first mutation in a presenilin gene
in a Spanish AD case, which is the third mutation detected for the
PS-2
gene.
Received: March 6, 1998 / Accepted: May 13, 1998 相似文献
19.