Phenotype-genotype relations in facioscapulohumeral muscular dystrophy type 1

Clinical Genetics
Karlien MulCorinne G Horlings

Abstract

To determine how much of the clinical variability in facioscapulohumeral muscular dystrophy type 1 (FSHD1) can be explained by the D4Z4 repeat array size, D4Z4 methylation and familial factors, we included 152 carriers of an FSHD1 allele (23 single cases, 129 familial cases from 37 families) and performed state-of-the-art genetic testing, extensive clinical evaluation and quantitative muscle MRI. Familial factors accounted for 50% of the variance in disease severity (FSHD clinical score). The explained variance by the D4Z4 repeat array size for disease severity was limited (approximately 10%), and varied per body region (facial muscles, upper and lower extremities approximately 30%, 15% and 3%, respectively). Unaffected gene carriers had longer repeat array sizes compared to symptomatic individuals (7.3 vs 6.0 units, P = 0.000) and slightly higher Delta1 methylation levels (D4Z4 methylation corrected for repeat size, 0.96 vs -2.46, P = 0.048). The D4Z4 repeat array size and D4Z4 methylation contribute to variability in disease severity and penetrance, but other disease modifying factors must be involved as well. The larger effect of the D4Z4 repeat array on facial muscle involvement suggests that these muscles are more sensitiv...Continue Reading

References

Jun 23, 2000·Journal of Neurology, Neurosurgery, and Psychiatry·A J van der KooiM de Visser
Dec 9, 2003·Neuromuscular Disorders : NMD·M M O ToniniM Zatz
Jan 20, 2004·Journal of Medical Genetics·K GotoY K Hayashi
Aug 18, 2005·Neuromuscular Disorders : NMD·Carole BérardUNKNOWN MFM Collaborative Study Group
Oct 10, 2007·American Journal of Human Genetics·Richard J L F LemmersSilvere M van der Maarel
Nov 7, 2007·Proceedings of the National Academy of Sciences of the United States of America·Manjusha DixitYi-Wen Chen
Mar 1, 2005·Journal of Clinical Neuromuscular Disease·Kevin J Felice, Charles H Whitaker
Jul 7, 2009·Ageing Research Reviews·Jennifer L KukRobert Ross
Aug 21, 2010·Science·Richard J L F LemmersSilvère M van der Maarel
Nov 10, 2010·PLoS Genetics·Lauren SniderDaniel G Miller
Dec 18, 2010·Journal of Neurology·Berit JordanStephan Zierz
Nov 15, 2011·Clinical Neurology and Neurosurgery·Ebe PastorelloCarlo P Trevisan
Aug 22, 2012·Muscle & Nerve·Anhar HassanNeeraj Kumar
Jul 23, 2013·Muscle & Nerve·Jeffrey M Statland, Rabi Tawil
Oct 1, 2013·American Journal of Human Genetics·Sabrina SacconiSilvère M van der Maarel
Aug 15, 2014·Neurology·Johanna C W DeenenBaziel G M van Engelen
Sep 27, 2014·Human Molecular Genetics·Richard J L F LemmersSilvère M van der Maarel
Feb 11, 2016·Practical Neurology·Karlien MulBaziel Gm van Engelen
May 8, 2016·American Journal of Human Genetics·Marlinde L van den BoogaardSilvère M van der Maarel
Mar 7, 2017·The Journal of Clinical Investigation·Emanuela TeveroniFabiola Moretti
Oct 17, 2017·Neurology·Karlien MulBaziel G M van Engelen
Dec 20, 2017·Nature Communications·Christopher R S BanerjiPeter S Zammit

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Citations

Dec 28, 2019·Statistical Methods in Medical Research·Marianne A JonkerMar Rodriguez Girondo
Apr 25, 2019·Annual Review of Genomics and Human Genetics·Charis L Himeda, Peter L Jones
Sep 22, 2020·Brain Communications·Rianne J M GoselinkThomas Theelen
Oct 29, 2020·Journal of Neurology·T G J LoonenK Mul
Nov 10, 2020·International Journal of Rehabilitation Research. Internationale Zeitschrift Für Rehabilitationsforschung. Revue Internationale De Recherches De Réadaptation·Karlien MulIngemar S J Merkies
Apr 11, 2021·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·Karlien MulIngemar S J Merkies

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