A family-based study into penetrance in facioscapulohumeral muscular dystrophy type 1

Neurology
Mariëlle WohlgemuthNicol C Voermans

Abstract

An observational cross-sectional study was conducted in a national facioscapulohumeral muscular dystrophy (FSHD) expertise center to estimate the penetrance of FSHD1 and to evaluate phenotype-genotype correlations. Ten FSHD1 probands carrying 4-9 D4Z4 unit alleles and 140 relatives were examined. All 150 participants were genetically characterized, including D4Z4 methylation levels in the mutation carriers. Mutation carriers were classified as (1) symptomatic: with symptoms of muscle weakness on history and muscle FSHD signs on examination; (2) asymptomatic: without symptoms of muscle weakness but with muscle FSHD signs on examination; and (3) nonpenetrant: without symptoms of muscle weakness on history and without muscle FSHD signs on examination. We assessed the relationship between age-corrected clinical severity score and repeat size, sex, and D4Z4 methylation levels. The maximum likelihood estimates of symptomatic and those of symptomatic plus asymptomatic FSHD showed that penetrance depends on repeat size and increases until late adulthood. We observed many asymptomatic carriers with subtle facial weakness with or without mild shoulder girdle weakness (25% [17/69]). Nonpenetrance was observed less frequently than in recen...Continue Reading

Associated Datasets

References

Jan 1, 1991·Neuromuscular Disorders : NMD·G W PadbergM Fardeau
Oct 22, 2003·Archives of Neurology·Michael KrasnianskiStephan Zierz
Dec 9, 2003·Neuromuscular Disorders : NMD·M M O ToniniM Zatz
Jan 20, 2004·Journal of Medical Genetics·K GotoY K Hayashi
May 22, 2004·American Journal of Human Genetics·Richard J L F LemmersSilvère M van der Maarel
Sep 24, 2005·Annals of Neurology·Petra G M van OverveldSilvère M van der Maarel
Sep 4, 2009·Human Mutation·Jessica C de GreefSilvère M van der Maarel
Aug 21, 2010·Science·Richard J L F LemmersSilvère M van der Maarel
Oct 27, 2010·Neurology·J C de GreefR Tawil
Nov 10, 2010·PLoS Genetics·Lauren SniderDaniel G Miller
Nov 15, 2011·Clinical Neurology and Neurosurgery·Ebe PastorelloCarlo P Trevisan
Feb 24, 2012·Neuromuscular Disorders : NMD·P SakellariouE Kanavakis
Jan 1, 1995·Muscle & Nerve. Supplement·G W PadbergL A Sandkuijl
Jul 18, 2014·Neurology·Marie-Cécile GaillardFrédérique Magdinier
Sep 27, 2014·Human Molecular Genetics·Richard J L F LemmersSilvère M van der Maarel
Mar 19, 2015·European Journal of Human Genetics : EJHG·Marlinde L van den BoogaardSilvère M van der Maarel
Feb 11, 2016·Practical Neurology·Karlien MulBaziel Gm van Engelen
Mar 5, 2016·Disability and Rehabilitation·Arjen BergsmaImelda J M de Groot
May 8, 2016·American Journal of Human Genetics·Marlinde L van den BoogaardSilvère M van der Maarel
Nov 8, 2017·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·J-J HeZ-Q Wang

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Citations

Oct 4, 2018·Human Molecular Genetics·Richard J L F LemmersSilvère M van der Maarel
Dec 28, 2019·Statistical Methods in Medical Research·Marianne A JonkerMar Rodriguez Girondo
Apr 14, 2019·Neurology·Sabrina SacconiSilvère M van der Maarel
Mar 15, 2020·Journal of Medical Genetics·Liangliang QiuZhiqiang Wang

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