Publications by authors named "Roland Spiegel"

8 Publications

  • Page 1 of 1

Collagen VI-Related Myopathy Caused by Compound Heterozygous Mutations of COL6A3 in a Consanguineous Kurdish Family.

J Clin Neuromuscul Dis 2021 Mar;22(3):173-179

Department of Neurology, University Hospital and University of Zurich, Zürich, Switzerland.

Abstract: Collagen VI-related myopathies are caused by mutations of COL6A1, COL6A2, and COL6A3 and present with a wide phenotypic spectrum ranging from severe Ulrich congenital muscular dystrophy to mild Bethlem myopathy. Here, we report a consanguineous Kurdish family with 3 siblings affected by autosomal-recessive Bethlem myopathy caused by compound heterozygous mutations of COL6A3. We found the previously described missense mutation c.7447A > G/p.(Lys2483Glu) and a novel large deletion encompassing the exon 1-39 of the COL6A3 gene. Apart from the classical clinical symptoms, all patients had keratoconus, which expands the phenotype of the collagen VI-related myopathies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/CND.0000000000000320DOI Listing
March 2021

Novel truncating mutations of causing congenital myopathy in a Swiss patient.

Neurol Genet 2020 Aug 9;6(4):e458. Epub 2020 Jun 9.

Department of Neurology (V.M., H.H.J.), University Hospital and University of Zurich; and Genetica (F.C., Y.H., R.S.), Human Genetics and Genetic Counselling Unit, Zurich, Switzerland.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/NXG.0000000000000458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7323478PMC
August 2020

Atypical periodic paralysis and myalgia: A novel phenotype.

Neurology 2018 01 3;90(5):e412-e418. Epub 2018 Jan 3.

From the MRC Centre for Neuromuscular Diseases (E.M., F.J., R.S.S., D.F., M.P., D.R.R., K.S., H.H., E.H., R.Q., J.L.H., M.G.H.), Department of Molecular Neuroscience, UCL Institute of Neurology and National Hospital for Neurology and Neurosurgery, Queen Square, London, UK; Neuromuscular Diseases Unit/ALS Clinic (C.N.), Kantonsspital St. Gallen, Switzerland; Neurogenetics Unit (R.S., H.H.) and Department of Neuropathology (J.L.H.), National Hospital for Neurology and Neurosurgery, Queen Square, London, UK; Human Genetics Laboratory Genetica (R.S.), Zurich, Switzerland; Genetics Department (R.M.), Viapath, Guy's Hospital, London; Wellcome Trust Centre for Mitochondrial Research (A.S.), University of Newcastle, Framlington Place, Newcastle Upon Tyne, UK; Institute of Pathology (E.H.), Belfast Health and Social Care Trust, Northern Ireland; Department of Neurology (J.P.), John Radcliffe Hospital, Oxford, UK; Departments of Biomedicine and Anesthesia (S.T.), Basel University Hospital, Switzerland; Department of Life Sciences (S.T.), Microbiology and Applied Pathology Section, University of Ferrara, Italy; Department of Paediatric Neurology (H.J.), Neuromuscular Service, Evelina Children's Hospital, St. Thomas' Hospital; and Department of Basic and Clinical Neuroscience (H.J.), Institute of Psychiatry, Psychology and Neuroscience, and Randall Division of Cell and Molecular Biophysics (H.J.), Muscle Signalling Section, King's College, London, UK.

Objective: To characterize the phenotype of patients with symptoms of periodic paralysis (PP) and ryanodine receptor () gene mutations.

Methods: Cases with a possible diagnosis of PP but additional clinicopathologic findings previously associated with related disorders were referred for a tertiary neuromuscular clinical assessment in which they underwent detailed clinical evaluation, including neurophysiologic assessment, muscle biopsy, and muscle MRI. Genetic analysis with next-generation sequencing and/or targeted Sanger sequencing was performed.

Results: Three cases with episodic muscle paralysis or weakness and additional findings compatible with a -related myopathy were identified. The McManis test, used in the diagnosis of PP, was positive in 2 of 3 cases. Genetic analysis of known PP genes was negative. analysis confirmed likely pathogenic variants in all 3 cases.

Conclusions: mutations can cause late-onset atypical PP both with and without associated myopathy. Myalgia and cramps are prominent features. The McManis test may be a useful diagnostic tool to indicate -associated PP. We propose that clinicopathologic features suggestive of -related disorders should be sought in genetically undefined PP cases and that gene testing be considered in those in whom mutations in , and have already been excluded.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/WNL.0000000000004894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5791790PMC
January 2018

Very-late-onset Friedreich ataxia with disturbing head tremor and without spinal atrophy--a case report.

Mov Disord 2008 May;23(7):1058-1059

Movement Disorders Center, Department of Neurology, Inselpital Bern University Hospital and University of Bern, Switzerland.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mds.21946DOI Listing
May 2008

Reliable detection of trisomy 21 using MALDI-TOF mass spectrometry.

Genet Med 2006 Nov;8(11):728-34

Laboratory for Prenatal Medicine University Women's Hospital, Department of Research Spitalstrasse 21, CH4031 Basel, Switzerland.

Purpose: Current diagnostic methods for chromosomal abnormalities rely mainly on karyotyping and occasionally fluorescent in situ hybridization or quantitative polymerase chain reaction. We describe an alternative molecular method for the detection of trisomy 21 involving mass spectrometric analysis of single nucleotide polymorphisms.

Methods: In collaboration with Sequenom, Inc., 350 blinded amniotic fluid, amniocyte culture, chorionic villus, or amniotic fluid supernatant samples were analyzed for trisomy 21 using SNP analysis and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Peak ratios were calculated for heterozygous genotypes and compared to control values generated from known euploid samples. An analytical algorithm using standard deviations from control values was used to determine the probability of a sample being affected or unaffected.

Results: Seventy-three trisomy 21 samples from among the 350 blinded samples were correctly identified. There were no false-positive or false-negative results among the complete trisomy 21 samples. One sample exhibiting mosaicism for trisomy 21 was identified as being unaffected.

Conclusions: MALDI-TOF mass spectrometry is a robust and reproducible method for the detection of trisomy 21. Its amenability to high-throughput analysis and high degree of multiplexing make it a potential future diagnostic tool for the detection of other aneuploidies as well.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/01.gim.0000245573.42908.34DOI Listing
November 2006

A novel complex mutation event in the peripherin/RDS gene in a family with retinal pattern dystrophy.

Retina 2006 Oct;26(8):947-53

Klinik Pallas, Department of Ophthalmology, Olten, Switzerland.

Purpose: To report a complex mutation in the peripherin/RDS gene found in a family in whom retinal pattern dystrophy is segregating as an autosomal dominant trait.

Methods: Clinical data were collected from family members of a large Swiss family affected by autosomal dominant retinal pattern dystrophy. Single strand conformation polymorphism (SSCP) analysis of the candidate gene peripherin/RDS and subsequent sequencing of the first exon were performed.

Results: Pattern dystrophy of the retina was suspected in 18 family members aged 30 years or older. Assuming a homogeneous phenotype, the candidate locus peripherin/RDS was investigated. SSCP analysis of the first exon of the peripherin/RDS gene showed an aberrant pattern in 18 affected individuals. Direct sequencing of polymerase chain reaction products detected a complex mutation, del265-268GCCA ins AGGGCC, leading to a stop codon at amino acid position 99.

Conclusion: To our knowledge, we report the first complex mutation in the peripherin/RDS gene as the cause of a mild macular phenotype, supporting the importance of molecular diagnosis in genetic counseling.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/01.iae.0000250010.60908.e3DOI Listing
October 2006

The spectrum of WRN mutations in Werner syndrome patients.

Hum Mutat 2006 Jun;27(6):558-67

Department of Pathology, University of Washington, Seattle, Washington 98195-7470, USA.

The International Registry of Werner syndrome (www.wernersyndrome.org) has been providing molecular diagnosis of the Werner syndrome (WS) for the past decade. The present communication summarizes, from among 99 WS subjects, the spectrum of 50 distinct mutations discovered by our group and by others since the WRN gene (also called RECQL2 or REQ3) was first cloned in 1996; 25 of these have not previously been published. All WRN mutations reported thus far have resulted in the elimination of the nuclear localization signal at the C-terminus of the protein, precluding functional interactions in the nucleus; thus, all could be classified as null mutations. We now report two new mutations in the N-terminus that result in instability of the WRN protein. Clinical data confirm that the most penetrant phenotype is bilateral ocular cataracts. Other cardinal signs were seen in more than 95% of the cases. The median age of death, previously reported to be in the range of 46-48 years, is 54 years. Lymphoblastoid cell lines (LCLs) have been cryopreserved from the majority of our index cases, including material from nuclear pedigrees. These, as well as inducible and complemented hTERT (catalytic subunit of human telomerase) immortalized skin fibroblast cell lines are available to qualified investigators.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/humu.20337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1868417PMC
June 2006