Clinical and genetic characterization of manifesting carriers of DMD mutations.

Neuromuscular Disorders : NMD
Payam SoltanzadehKevin M Flanigan

Abstract

Manifesting carriers of DMD gene mutations may present diagnostic challenges, particularly in the absence of a family history of dystrophinopathy. We review the clinical and genetic features in 15 manifesting carriers identified among 860 subjects within the United Dystrophinopathy Project, a large clinical dystrophinopathy cohort whose members undergo comprehensive DMD mutation analysis. We defined manifesting carriers as females with significant weakness, excluding those with only myalgias/cramps. DNA extracted from peripheral blood was used to study X-chromosome inactivation patterns. Among these manifesting carriers, age at symptom onset ranged from 2 to 47 years. Seven had no family history and eight had male relatives with Duchenne muscular dystrophy (DMD). Clinical severity among the manifesting carriers varied from a DMD-like progression to a very mild Becker muscular dystrophy-like phenotype. Eight had exonic deletions or duplications and six had point mutations. One patient had two mutations (an exonic deletion and a splice site mutation), consistent with a heterozygous compound state. The X-chromosome inactivation pattern was skewed toward non-random in four out of seven informative deletions or duplications but was ...Continue Reading

References

May 1, 1992·Neurology·E P HoffmanL P Rowland
Jul 17, 1999·Neuromuscular Disorders : NMD·E M HoogerwaardM de Visser
Mar 13, 2003·American Journal of Human Genetics·Kevin M FlaniganRobert B Weiss
Apr 4, 2003·American Journal of Medical Genetics. Part a·Anthonie J van EssenJohan T den Dunnen
Feb 22, 2005·American Journal of Medical Genetics. Part a·K M DentK M Flanigan
Dec 29, 2005·Neurology·Edo M HoogerwaardMarianne de Visser
Jul 11, 2006·European Journal of Human Genetics : EJHG·Gun Peggy S KnudsenKaren Helene Orstavik
Dec 22, 2007·The Journal of Clinical Investigation·Véronique BolducLambert Busque
Dec 25, 2007·Journal of Medical Genetics·D C BittelM G Butler

❮ Previous
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Citations

Jan 10, 2013·European Journal of Human Genetics : EJHG·Sandra MercierIsabelle Desguerre
May 16, 2012·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·G TascaE Ricci
Oct 25, 2012·Orphanet Journal of Rare Diseases·Jonàs Juan-MateuPia Gallano
Feb 24, 2012·PloS One·Maaike van PuttenAnnemieke Aartsma-Rus
Apr 2, 2014·Skeletal Muscle·Maria Victoria NeguemborDavide Gabellini
Jul 11, 2014·Journal of Cardiovascular Magnetic Resonance : Official Journal of the Society for Cardiovascular Magnetic Resonance·Vincenzo GiglioMarco Di Gennaro
Sep 11, 2012·European Journal of Paediatric Neurology : EJPN : Official Journal of the European Paediatric Neurology Society·Marcio LeyserOsvaldo J M Nascimento
Sep 4, 2012·Physical Medicine and Rehabilitation Clinics of North America·W David Arnold, Kevin M Flanigan
Apr 28, 2012·Medicina clínica·Jonàs Juan-MateuUNKNOWN Grupo AEGH/CIBERER
May 18, 2012·International Journal of Cardiology·Josef FinstererChristoph Schukro
Jan 13, 2016·Journal of Medical Genetics·Annemieke Aartsma-RusKate Bushby
Nov 22, 2012·Muscle & Nerve·Andrew R FindlayKevin M Flanigan
Aug 16, 2014·American Journal of Medical Genetics. Part a·Lauren ImbornoniChristopher Cunniff
Apr 23, 2015·Neuromuscular Disorders : NMD·Carola Hedberg OldforsAnders Oldfors
Nov 28, 2012·International Journal of Cardiology·Josef FinstererMartin Gencik
Oct 19, 2013·Journal of the Neurological Sciences·Florencia GilibertoIrene Szijan
Jan 17, 2016·Archives de pédiatrie : organe officiel de la Sociéte française de pédiatrie·A MagotY Péréon
Apr 26, 2011·Molecular Genetics and Metabolism·Abdul Qawee RaniMasafumi Matsuo
Feb 10, 2017·The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques·Ana CottaAntonio Pedro Vargas
Oct 21, 2016·Muscle & Nerve·Thomas MccaffreyJohn P Bourke
May 21, 2017·Skeletal Muscle·Joe N Kornegay
May 22, 2017·The Journal of Allergy and Clinical Immunology·Beatriz E MarcianoSteven M Holland
Oct 14, 2017·European Journal of Clinical Investigation·Sophie MavrogeniGeorge P Chrousos
Mar 13, 2018·Internal Medicine·Michio KobayashiEn Kimura
Jul 18, 2018·Annals of Neurology·Robert B WeissUNKNOWN United Dystrophinopathy Project
May 30, 2015·Journal of Clinical Neurology·Seung Ha LeeYoung Chul Choi
Aug 5, 2017·Journal of Cardiovascular Translational Research·Yi Zhen Joan Lee, Daniel P Judge
Aug 3, 2019·Journal of Genetic Counseling·Lauren EekhoffEloise J Prijoles
Dec 7, 2013·Continuum : Lifelong Learning in Neurology·Matthew P Wicklund
Sep 5, 2020·Pediatric Pulmonology·Nicolas J Abreu, Megan A Waldrop
Jun 1, 2017·International Journal of Neonatal Screening·Samiah A Al-ZaidyJerry R Mendell
Dec 19, 2019·Journal of Cachexia, Sarcopenia and Muscle·Tirsa L E van WesteringThomas C Roberts

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