Evidence map›Paper›PMID 27316240›Full record

ArticleNeurology2016

Uniparental disomy of chromosome 16 unmasks recessive mutations of FA2H/SPG35 in 4 families.

Anne S Soehn, Tim W Rattay, Stefanie Beck-Wödl, Karin Schäferhoff, David Monk, Marion Döbler-Neumann, Konstanze Hörtnagel, Agatha Schlüter, Montserrat Ruiz, Aurora Pujol and 5 more

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In one paragraph

Article in Neurology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 1 pooled it
2.0field-weighted citation impact, top 15% of its field
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

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3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.

  1. Pooled it
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  3. Clinical, Radiological, and Genetic Profile of Patients withTremor and other hyperkinetic movements (New York, N.Y.) · 2026
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  8. Case Report: A Novel Homozygous Mutation inFrontiers in genetics · 2021
    Article
  9. Article
  10. Article
  11. Review
  12. Review
  13. Article
  14. Overcoming the divide between ataxias and spastic paraplegias: Shared phenotypes, genes, and pathways.Movement disorders : official journal of the Movement Disorder Society · 2017
    Review
  15. Article
  16. Article
4 · The record

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5 · Who and what money

Authors and funding

15 authors at 1 institution in 1 country.

Anne S SoehnFrom the Institute of Medical Genetics and Applied Genomics (A.S.S., S.B.-W., K.S., O.R., P.B.) and Department of Neurology and Hertie Institute for Clinical Brain Research (T.W.R., R.S., L.S.), University of Tübingen; German Center of Neurodegenerative Diseases (DZNE) (T.W.R., R.S.), Tübingen, Germany; Imprinting and Cancer Group (D.M.), Cancer Epigenetic and Biology Program, Institut d'Investigació Biomedica de Bellvitge, Hospital Duran i Reynals, Barcelona, Spain; Department of Neuropediatrics (M.D.-N.), Tübingen University School of Medicine; CeGaT GmbH (K.H.), Tübingen, Germany; Neurometabolic Diseases Laboratory (A.S., M.R., A.P.), Institut d'Investigació Biomedica de Bellvitge IDIBELL, Hospital Duran i Reynals, Barcelona; Centre for Biomedical Research on Rare Diseases (CIBERER) (A.S., M.R., A.P.), Institute Carlos III, Madrid; Catalan Institution for Research and Advanced Studies (ICREA) (A.P.), Barcelona, Spain; and Hussman Institute for Human Genomics (S.Z., R.S.), University of Miami Miller School of Medicine, FL.
Tim W RattayFrom the Institute of Medical Genetics and Applied Genomics (A.S.S., S.B.-W., K.S., O.R., P.B.) and Department of Neurology and Hertie Institute for Clinical Brain Research (T.W.R., R.S., L.S.), University of Tübingen; German Center of Neurodegenerative Diseases (DZNE) (T.W.R., R.S.), Tübingen, Germany; Imprinting and Cancer Group (D.M.), Cancer Epigenetic and Biology Program, Institut d'Investigació Biomedica de Bellvitge, Hospital Duran i Reynals, Barcelona, Spain; Department of Neuropediatrics (M.D.-N.), Tübingen University School of Medicine; CeGaT GmbH (K.H.), Tübingen, Germany; Neurometabolic Diseases Laboratory (A.S., M.R., A.P.), Institut d'Investigació Biomedica de Bellvitge IDIBELL, Hospital Duran i Reynals, Barcelona; Centre for Biomedical Research on Rare Diseases (CIBERER) (A.S., M.R., A.P.), Institute Carlos III, Madrid; Catalan Institution for Research and Advanced Studies (ICREA) (A.P.), Barcelona, Spain; and Hussman Institute for Human Genomics (S.Z., R.S.), University of Miami Miller School of Medicine, FL.
Stefanie Beck-WödlFrom the Institute of Medical Genetics and Applied Genomics (A.S.S., S.B.-W., K.S., O.R., P.B.) and Department of Neurology and Hertie Institute for Clinical Brain Research (T.W.R., R.S., L.S.), University of Tübingen; German Center of Neurodegenerative Diseases (DZNE) (T.W.R., R.S.), Tübingen, Germany; Imprinting and Cancer Group (D.M.), Cancer Epigenetic and Biology Program, Institut d'Investigació Biomedica de Bellvitge, Hospital Duran i Reynals, Barcelona, Spain; Department of Neuropediatrics (M.D.-N.), Tübingen University School of Medicine; CeGaT GmbH (K.H.), Tübingen, Germany; Neurometabolic Diseases Laboratory (A.S., M.R., A.P.), Institut d'Investigació Biomedica de Bellvitge IDIBELL, Hospital Duran i Reynals, Barcelona; Centre for Biomedical Research on Rare Diseases (CIBERER) (A.S., M.R., A.P.), Institute Carlos III, Madrid; Catalan Institution for Research and Advanced Studies (ICREA) (A.P.), Barcelona, Spain; and Hussman Institute for Human Genomics (S.Z., R.S.), University of Miami Miller School of Medicine, FL.
Karin SchäferhoffFrom the Institute of Medical Genetics and Applied Genomics (A.S.S., S.B.-W., K.S., O.R., P.B.) and Department of Neurology and Hertie Institute for Clinical Brain Research (T.W.R., R.S., L.S.), University of Tübingen; German Center of Neurodegenerative Diseases (DZNE) (T.W.R., R.S.), Tübingen, Germany; Imprinting and Cancer Group (D.M.), Cancer Epigenetic and Biology Program, Institut d'Investigació Biomedica de Bellvitge, Hospital Duran i Reynals, Barcelona, Spain; Department of Neuropediatrics (M.D.-N.), Tübingen University School of Medicine; CeGaT GmbH (K.H.), Tübingen, Germany; Neurometabolic Diseases Laboratory (A.S., M.R., A.P.), Institut d'Investigació Biomedica de Bellvitge IDIBELL, Hospital Duran i Reynals, Barcelona; Centre for Biomedical Research on Rare Diseases (CIBERER) (A.S., M.R., A.P.), Institute Carlos III, Madrid; Catalan Institution for Research and Advanced Studies (ICREA) (A.P.), Barcelona, Spain; and Hussman Institute for Human Genomics (S.Z., R.S.), University of Miami Miller School of Medicine, FL.
David MonkFrom the Institute of Medical Genetics and Applied Genomics (A.S.S., S.B.-W., K.S., O.R., P.B.) and Department of Neurology and Hertie Institute for Clinical Brain Research (T.W.R., R.S., L.S.), University of Tübingen; German Center of Neurodegenerative Diseases (DZNE) (T.W.R., R.S.), Tübingen, Germany; Imprinting and Cancer Group (D.M.), Cancer Epigenetic and Biology Program, Institut d'Investigació Biomedica de Bellvitge, Hospital Duran i Reynals, Barcelona, Spain; Department of Neuropediatrics (M.D.-N.), Tübingen University School of Medicine; CeGaT GmbH (K.H.), Tübingen, Germany; Neurometabolic Diseases Laboratory (A.S., M.R., A.P.), Institut d'Investigació Biomedica de Bellvitge IDIBELL, Hospital Duran i Reynals, Barcelona; Centre for Biomedical Research on Rare Diseases (CIBERER) (A.S., M.R., A.P.), Institute Carlos III, Madrid; Catalan Institution for Research and Advanced Studies (ICREA) (A.P.), Barcelona, Spain; and Hussman Institute for Human Genomics (S.Z., R.S.), University of Miami Miller School of Medicine, FL.
Marion Döbler-NeumannFrom the Institute of Medical Genetics and Applied Genomics (A.S.S., S.B.-W., K.S., O.R., P.B.) and Department of Neurology and Hertie Institute for Clinical Brain Research (T.W.R., R.S., L.S.), University of Tübingen; German Center of Neurodegenerative Diseases (DZNE) (T.W.R., R.S.), Tübingen, Germany; Imprinting and Cancer Group (D.M.), Cancer Epigenetic and Biology Program, Institut d'Investigació Biomedica de Bellvitge, Hospital Duran i Reynals, Barcelona, Spain; Department of Neuropediatrics (M.D.-N.), Tübingen University School of Medicine; CeGaT GmbH (K.H.), Tübingen, Germany; Neurometabolic Diseases Laboratory (A.S., M.R., A.P.), Institut d'Investigació Biomedica de Bellvitge IDIBELL, Hospital Duran i Reynals, Barcelona; Centre for Biomedical Research on Rare Diseases (CIBERER) (A.S., M.R., A.P.), Institute Carlos III, Madrid; Catalan Institution for Research and Advanced Studies (ICREA) (A.P.), Barcelona, Spain; and Hussman Institute for Human Genomics (S.Z., R.S.), University of Miami Miller School of Medicine, FL.
Konstanze HörtnagelFrom the Institute of Medical Genetics and Applied Genomics (A.S.S., S.B.-W., K.S., O.R., P.B.) and Department of Neurology and Hertie Institute for Clinical Brain Research (T.W.R., R.S., L.S.), University of Tübingen; German Center of Neurodegenerative Diseases (DZNE) (T.W.R., R.S.), Tübingen, Germany; Imprinting and Cancer Group (D.M.), Cancer Epigenetic and Biology Program, Institut d'Investigació Biomedica de Bellvitge, Hospital Duran i Reynals, Barcelona, Spain; Department of Neuropediatrics (M.D.-N.), Tübingen University School of Medicine; CeGaT GmbH (K.H.), Tübingen, Germany; Neurometabolic Diseases Laboratory (A.S., M.R., A.P.), Institut d'Investigació Biomedica de Bellvitge IDIBELL, Hospital Duran i Reynals, Barcelona; Centre for Biomedical Research on Rare Diseases (CIBERER) (A.S., M.R., A.P.), Institute Carlos III, Madrid; Catalan Institution for Research and Advanced Studies (ICREA) (A.P.), Barcelona, Spain; and Hussman Institute for Human Genomics (S.Z., R.S.), University of Miami Miller School of Medicine, FL.
Agatha SchlüterFrom the Institute of Medical Genetics and Applied Genomics (A.S.S., S.B.-W., K.S., O.R., P.B.) and Department of Neurology and Hertie Institute for Clinical Brain Research (T.W.R., R.S., L.S.), University of Tübingen; German Center of Neurodegenerative Diseases (DZNE) (T.W.R., R.S.), Tübingen, Germany; Imprinting and Cancer Group (D.M.), Cancer Epigenetic and Biology Program, Institut d'Investigació Biomedica de Bellvitge, Hospital Duran i Reynals, Barcelona, Spain; Department of Neuropediatrics (M.D.-N.), Tübingen University School of Medicine; CeGaT GmbH (K.H.), Tübingen, Germany; Neurometabolic Diseases Laboratory (A.S., M.R., A.P.), Institut d'Investigació Biomedica de Bellvitge IDIBELL, Hospital Duran i Reynals, Barcelona; Centre for Biomedical Research on Rare Diseases (CIBERER) (A.S., M.R., A.P.), Institute Carlos III, Madrid; Catalan Institution for Research and Advanced Studies (ICREA) (A.P.), Barcelona, Spain; and Hussman Institute for Human Genomics (S.Z., R.S.), University of Miami Miller School of Medicine, FL.
Montserrat RuizFrom the Institute of Medical Genetics and Applied Genomics (A.S.S., S.B.-W., K.S., O.R., P.B.) and Department of Neurology and Hertie Institute for Clinical Brain Research (T.W.R., R.S., L.S.), University of Tübingen; German Center of Neurodegenerative Diseases (DZNE) (T.W.R., R.S.), Tübingen, Germany; Imprinting and Cancer Group (D.M.), Cancer Epigenetic and Biology Program, Institut d'Investigació Biomedica de Bellvitge, Hospital Duran i Reynals, Barcelona, Spain; Department of Neuropediatrics (M.D.-N.), Tübingen University School of Medicine; CeGaT GmbH (K.H.), Tübingen, Germany; Neurometabolic Diseases Laboratory (A.S., M.R., A.P.), Institut d'Investigació Biomedica de Bellvitge IDIBELL, Hospital Duran i Reynals, Barcelona; Centre for Biomedical Research on Rare Diseases (CIBERER) (A.S., M.R., A.P.), Institute Carlos III, Madrid; Catalan Institution for Research and Advanced Studies (ICREA) (A.P.), Barcelona, Spain; and Hussman Institute for Human Genomics (S.Z., R.S.), University of Miami Miller School of Medicine, FL.
Aurora PujolFrom the Institute of Medical Genetics and Applied Genomics (A.S.S., S.B.-W., K.S., O.R., P.B.) and Department of Neurology and Hertie Institute for Clinical Brain Research (T.W.R., R.S., L.S.), University of Tübingen; German Center of Neurodegenerative Diseases (DZNE) (T.W.R., R.S.), Tübingen, Germany; Imprinting and Cancer Group (D.M.), Cancer Epigenetic and Biology Program, Institut d'Investigació Biomedica de Bellvitge, Hospital Duran i Reynals, Barcelona, Spain; Department of Neuropediatrics (M.D.-N.), Tübingen University School of Medicine; CeGaT GmbH (K.H.), Tübingen, Germany; Neurometabolic Diseases Laboratory (A.S., M.R., A.P.), Institut d'Investigació Biomedica de Bellvitge IDIBELL, Hospital Duran i Reynals, Barcelona; Centre for Biomedical Research on Rare Diseases (CIBERER) (A.S., M.R., A.P.), Institute Carlos III, Madrid; Catalan Institution for Research and Advanced Studies (ICREA) (A.P.), Barcelona, Spain; and Hussman Institute for Human Genomics (S.Z., R.S.), University of Miami Miller School of Medicine, FL.
Stephan ZüchnerFrom the Institute of Medical Genetics and Applied Genomics (A.S.S., S.B.-W., K.S., O.R., P.B.) and Department of Neurology and Hertie Institute for Clinical Brain Research (T.W.R., R.S., L.S.), University of Tübingen; German Center of Neurodegenerative Diseases (DZNE) (T.W.R., R.S.), Tübingen, Germany; Imprinting and Cancer Group (D.M.), Cancer Epigenetic and Biology Program, Institut d'Investigació Biomedica de Bellvitge, Hospital Duran i Reynals, Barcelona, Spain; Department of Neuropediatrics (M.D.-N.), Tübingen University School of Medicine; CeGaT GmbH (K.H.), Tübingen, Germany; Neurometabolic Diseases Laboratory (A.S., M.R., A.P.), Institut d'Investigació Biomedica de Bellvitge IDIBELL, Hospital Duran i Reynals, Barcelona; Centre for Biomedical Research on Rare Diseases (CIBERER) (A.S., M.R., A.P.), Institute Carlos III, Madrid; Catalan Institution for Research and Advanced Studies (ICREA) (A.P.), Barcelona, Spain; and Hussman Institute for Human Genomics (S.Z., R.S.), University of Miami Miller School of Medicine, FL.
Olaf RiessFrom the Institute of Medical Genetics and Applied Genomics (A.S.S., S.B.-W., K.S., O.R., P.B.) and Department of Neurology and Hertie Institute for Clinical Brain Research (T.W.R., R.S., L.S.), University of Tübingen; German Center of Neurodegenerative Diseases (DZNE) (T.W.R., R.S.), Tübingen, Germany; Imprinting and Cancer Group (D.M.), Cancer Epigenetic and Biology Program, Institut d'Investigació Biomedica de Bellvitge, Hospital Duran i Reynals, Barcelona, Spain; Department of Neuropediatrics (M.D.-N.), Tübingen University School of Medicine; CeGaT GmbH (K.H.), Tübingen, Germany; Neurometabolic Diseases Laboratory (A.S., M.R., A.P.), Institut d'Investigació Biomedica de Bellvitge IDIBELL, Hospital Duran i Reynals, Barcelona; Centre for Biomedical Research on Rare Diseases (CIBERER) (A.S., M.R., A.P.), Institute Carlos III, Madrid; Catalan Institution for Research and Advanced Studies (ICREA) (A.P.), Barcelona, Spain; and Hussman Institute for Human Genomics (S.Z., R.S.), University of Miami Miller School of Medicine, FL.
Rebecca SchüleFrom the Institute of Medical Genetics and Applied Genomics (A.S.S., S.B.-W., K.S., O.R., P.B.) and Department of Neurology and Hertie Institute for Clinical Brain Research (T.W.R., R.S., L.S.), University of Tübingen; German Center of Neurodegenerative Diseases (DZNE) (T.W.R., R.S.), Tübingen, Germany; Imprinting and Cancer Group (D.M.), Cancer Epigenetic and Biology Program, Institut d'Investigació Biomedica de Bellvitge, Hospital Duran i Reynals, Barcelona, Spain; Department of Neuropediatrics (M.D.-N.), Tübingen University School of Medicine; CeGaT GmbH (K.H.), Tübingen, Germany; Neurometabolic Diseases Laboratory (A.S., M.R., A.P.), Institut d'Investigació Biomedica de Bellvitge IDIBELL, Hospital Duran i Reynals, Barcelona; Centre for Biomedical Research on Rare Diseases (CIBERER) (A.S., M.R., A.P.), Institute Carlos III, Madrid; Catalan Institution for Research and Advanced Studies (ICREA) (A.P.), Barcelona, Spain; and Hussman Institute for Human Genomics (S.Z., R.S.), University of Miami Miller School of Medicine, FL.
Peter BauerFrom the Institute of Medical Genetics and Applied Genomics (A.S.S., S.B.-W., K.S., O.R., P.B.) and Department of Neurology and Hertie Institute for Clinical Brain Research (T.W.R., R.S., L.S.), University of Tübingen; German Center of Neurodegenerative Diseases (DZNE) (T.W.R., R.S.), Tübingen, Germany; Imprinting and Cancer Group (D.M.), Cancer Epigenetic and Biology Program, Institut d'Investigació Biomedica de Bellvitge, Hospital Duran i Reynals, Barcelona, Spain; Department of Neuropediatrics (M.D.-N.), Tübingen University School of Medicine; CeGaT GmbH (K.H.), Tübingen, Germany; Neurometabolic Diseases Laboratory (A.S., M.R., A.P.), Institut d'Investigació Biomedica de Bellvitge IDIBELL, Hospital Duran i Reynals, Barcelona; Centre for Biomedical Research on Rare Diseases (CIBERER) (A.S., M.R., A.P.), Institute Carlos III, Madrid; Catalan Institution for Research and Advanced Studies (ICREA) (A.P.), Barcelona, Spain; and Hussman Institute for Human Genomics (S.Z., R.S.), University of Miami Miller School of Medicine, FL. peter.bauer@med.uni-tuebingen.de.
Ludger SchölsFrom the Institute of Medical Genetics and Applied Genomics (A.S.S., S.B.-W., K.S., O.R., P.B.) and Department of Neurology and Hertie Institute for Clinical Brain Research (T.W.R., R.S., L.S.), University of Tübingen; German Center of Neurodegenerative Diseases (DZNE) (T.W.R., R.S.), Tübingen, Germany; Imprinting and Cancer Group (D.M.), Cancer Epigenetic and Biology Program, Institut d'Investigació Biomedica de Bellvitge, Hospital Duran i Reynals, Barcelona, Spain; Department of Neuropediatrics (M.D.-N.), Tübingen University School of Medicine; CeGaT GmbH (K.H.), Tübingen, Germany; Neurometabolic Diseases Laboratory (A.S., M.R., A.P.), Institut d'Investigació Biomedica de Bellvitge IDIBELL, Hospital Duran i Reynals, Barcelona; Centre for Biomedical Research on Rare Diseases (CIBERER) (A.S., M.R., A.P.), Institute Carlos III, Madrid; Catalan Institution for Research and Advanced Studies (ICREA) (A.P.), Barcelona, Spain; and Hussman Institute for Human Genomics (S.Z., R.S.), University of Miami Miller School of Medicine, FL.
Institució Catalana de Recerca i Estudis Avançats · ES

Funding

GENOME STUDIES IN HEREDITARY SPASTIC PARAPLEGIA - beyond the exomeR01NS072248 · NINDS · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI Stephan Zuchner · 2011 to 2026
$9.2M
Genomic Studies in Charcot-Marie-Tooth DiseaseR01NS075764 · NINDS · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI SHY, MICHAEL E., ZUCHNER, STEPHAN · 2012 to 2016
$3.0M
Molecular And Genetic Analysis Of Autosomal Dominant Spastic ParaplegiaR01NS054132 · NINDS · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI ZUCHNER, STEPHAN · 2008 to 2011
$1.3M
NINDS NIH HHS R01 NS054132NINDS NIH HHS R01 NS072248NINDS NIH HHS R01 NS075764
6 · The paper itself

Abstract

objectiveIdentifying an intriguing mechanism for unmasking recessive hereditary spastic paraplegias.

methodHerein, we describe 4 novel homozygous FA2H mutations in 4 nonconsanguineous families detected by whole-exome sequencing or a targeted gene panel analysis providing high coverage of all known hereditary spastic paraplegia genes.

resultsSegregation analysis revealed in all cases only one parent as a heterozygous mutation carrier whereas the other parent did not carry FA2H mutations. A macro deletion within FA2H, which could have caused a hemizygous genotype, was excluded by multiplex ligation-dependent probe amplification in all cases. Finally, a microsatellite array revealed uniparental disomy (UPD) in all 4 families leading to homozygous FA2H mutations. UPD was confirmed by microarray analyses and methylation profiling.

conclusionUPD has rarely been described as causative mechanism in neurodegenerative diseases. Of note, we identified this mode of inheritance in 4 families with the rare diagnosis of spastic paraplegia type 35 (SPG35). Since UPD seems to be a relevant factor in SPG35 and probably additional autosomal recessive diseases, we recommend segregation analysis especially in nonconsanguineous homozygous index cases to unravel UPD as mutational mechanism. This finding may bear major repercussion for genetic counseling, given the markedly reduced risk of recurrence for affected families.

Indexed as

Chromosomes, Human, Pair 16Uniparental DisomyAdolescentChildCodon, NonsenseFamilyFemaleHeredodegenerative Disorders, Nervous SystemHumansMaleMicrosatellite RepeatsMixed Function OxygenasesMutation, MissenseCodon, Nonsensefatty acid alpha-hydroxylaseMixed Function Oxygenases

Identifiers

PMID27316240
PMCPMC4940069
OpenAlexW2424429388

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