Genetic Patterns of Selected Muscular Dystrophies in the Muscular Dystrophy Surveillance, Tracking, and Research Network.

Journal

Neurology. Genetics
ISSN: 2376-7839
Titre abrégé: Neurol Genet
Pays: United States
ID NLM: 101671068

Informations de publication

Date de publication:
Dec 2023
Historique:
received: 22 06 2023
accepted: 29 09 2023
medline: 4 12 2023
pubmed: 4 12 2023
entrez: 4 12 2023
Statut: epublish

Résumé

To report the genetic etiologies of Emery-Dreifuss muscular dystrophy (EDMD), limb-girdle muscular dystrophy (LGMD), congenital muscular dystrophy (CMD), and distal muscular dystrophy (DD) in 6 geographically defined areas of the United States. This was a cross-sectional, population-based study in which we studied the genes and variants associated with muscular dystrophy in individuals who were diagnosed with and received care for EDMD, LGMD, CMD, and DD from January 1, 2008, through December 31, 2016, in the 6 areas of the United States covered by the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STAR Among 243 individuals with definite or probable muscular dystrophy, LGMD was the most common diagnosis (138 cases), followed by CMD (62 cases), DD (22 cases), and EDMD (21 cases). There was a higher proportion of male individuals compared with female individuals, which persisted after excluding X-linked genes ( This study is distinct for being an examination of 4 types of muscular dystrophies in selected geographic areas of the United States. The striking proportion of resolved VUSs demonstrates the value of periodic re-examinations of these variants. Such re-examinations will resolve some genetic diagnostic ambiguities before initiating repeat testing or more invasive diagnostic procedures such as muscle biopsy. The presence of monoallelic pathogenic variants in recessive genes in our cohort indicates that some individuals with muscular dystrophy continue to face incomplete genetic diagnoses; further refinements in genetic knowledge and diagnostic approaches will optimize diagnostic information for these individuals.

Sections du résumé

Background and Objectives UNASSIGNED
To report the genetic etiologies of Emery-Dreifuss muscular dystrophy (EDMD), limb-girdle muscular dystrophy (LGMD), congenital muscular dystrophy (CMD), and distal muscular dystrophy (DD) in 6 geographically defined areas of the United States.
Methods UNASSIGNED
This was a cross-sectional, population-based study in which we studied the genes and variants associated with muscular dystrophy in individuals who were diagnosed with and received care for EDMD, LGMD, CMD, and DD from January 1, 2008, through December 31, 2016, in the 6 areas of the United States covered by the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STAR
Results UNASSIGNED
Among 243 individuals with definite or probable muscular dystrophy, LGMD was the most common diagnosis (138 cases), followed by CMD (62 cases), DD (22 cases), and EDMD (21 cases). There was a higher proportion of male individuals compared with female individuals, which persisted after excluding X-linked genes (
Discussion UNASSIGNED
This study is distinct for being an examination of 4 types of muscular dystrophies in selected geographic areas of the United States. The striking proportion of resolved VUSs demonstrates the value of periodic re-examinations of these variants. Such re-examinations will resolve some genetic diagnostic ambiguities before initiating repeat testing or more invasive diagnostic procedures such as muscle biopsy. The presence of monoallelic pathogenic variants in recessive genes in our cohort indicates that some individuals with muscular dystrophy continue to face incomplete genetic diagnoses; further refinements in genetic knowledge and diagnostic approaches will optimize diagnostic information for these individuals.

Identifiants

DOI: 10.1212/NXG.0000000000200113 PMID: 38045992 PMC: PMC10692796
pubmed: 38045992
doi: 10.1212/NXG.0000000000200113
pii: NXG-2023-000205
pmc: PMC10692796
doi:

Types de publication

Journal Article

Langues

eng

Pagination

e200113

Informations de copyright

Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Déclaration de conflit d'intérêts

P.B. Kang has served on advisory boards for Sarepta Therapeutics, NS Pharma, and Teneofour; and has served as a consultant for Novartis and Neurogene. M. Jorand-Fletcher reports no disclosures. W. Zhang reports no disclosures. S.W. McDermott reports no disclosures. R. Berry reports no disclosures. C. Chambers reports no disclosures. K.N. Wong reports no disclosures. Y. Mohamed reports no disclosures. S. Thomas reports no disclosures. Y.S. Venkatesh reports no disclosures. C. Westfield reports no disclosures. N. Whitehead reports no disclosures. N.E. Johnson has received grant funding from the NIH (R01 NS104010 and R21 TR003184), CDC (U01 DD001242), and the FDA (R01 FD006071). He receives research funds from Dyne, AveXis, Vertex Pharmaceuticals, Fulcrum Therapeutics, ML Bio, Sarepta, Triplet Therapeutics, Avidity Biosciences, and AMO Pharma. He has provided consultation for AMO Pharma, AveXis, Fulcrum Therapeutics, Dyne, Avidity, Vertex, and Entrada. He receives licensing fees from the University of Rochester for the CCMDHI and CMTHI. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/NG.

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Auteurs

Peter B Kang (PB)

From the Paul & Sheila Wellstone Muscular Dystrophy Center (P.B.K.), Department of Neurology, and Institute for Translational Neuroscience, University of Minnesota, Minneapolis; Department of Pediatrics (M.J.-F., Y.M.), University of Florida College of Medicine, Gainesville; Department of Epidemiology and Biostatistics (W.Z.), University of South Carolina, Columbia; Department of Environmental, Occupational, and Geospatial Health Sciences (S.W.M.), Graduate School of Public Health and Health Policy, City University of New York; Division of Population Health Surveillance (R.B., C.W.), Bureau of Maternal and Child Health, South Carolina Department of Health and Environmental Control, Columbia; Department of Human and Molecular Genetics (C.C.), Virginia Commonwealth University, Richmond; Department of Pediatrics (K.N.W.), University of Utah, Salt Lake City; New York State Department of Health (S.T.), Albany; Department of Neurology (Y.S.V.), University of South Carolina, Columbia; RTI International (N.W.), Research Triangle Park, NC; and Department of Neurology (N.E.J.), Virginia Commonwealth University, Richmond.
ORCID: 0000-0002-4270-7325

Magali Jorand-Fletcher (M)

From the Paul & Sheila Wellstone Muscular Dystrophy Center (P.B.K.), Department of Neurology, and Institute for Translational Neuroscience, University of Minnesota, Minneapolis; Department of Pediatrics (M.J.-F., Y.M.), University of Florida College of Medicine, Gainesville; Department of Epidemiology and Biostatistics (W.Z.), University of South Carolina, Columbia; Department of Environmental, Occupational, and Geospatial Health Sciences (S.W.M.), Graduate School of Public Health and Health Policy, City University of New York; Division of Population Health Surveillance (R.B., C.W.), Bureau of Maternal and Child Health, South Carolina Department of Health and Environmental Control, Columbia; Department of Human and Molecular Genetics (C.C.), Virginia Commonwealth University, Richmond; Department of Pediatrics (K.N.W.), University of Utah, Salt Lake City; New York State Department of Health (S.T.), Albany; Department of Neurology (Y.S.V.), University of South Carolina, Columbia; RTI International (N.W.), Research Triangle Park, NC; and Department of Neurology (N.E.J.), Virginia Commonwealth University, Richmond.
ORCID: 0009-0006-7369-6696

Wanfang Zhang (W)

From the Paul & Sheila Wellstone Muscular Dystrophy Center (P.B.K.), Department of Neurology, and Institute for Translational Neuroscience, University of Minnesota, Minneapolis; Department of Pediatrics (M.J.-F., Y.M.), University of Florida College of Medicine, Gainesville; Department of Epidemiology and Biostatistics (W.Z.), University of South Carolina, Columbia; Department of Environmental, Occupational, and Geospatial Health Sciences (S.W.M.), Graduate School of Public Health and Health Policy, City University of New York; Division of Population Health Surveillance (R.B., C.W.), Bureau of Maternal and Child Health, South Carolina Department of Health and Environmental Control, Columbia; Department of Human and Molecular Genetics (C.C.), Virginia Commonwealth University, Richmond; Department of Pediatrics (K.N.W.), University of Utah, Salt Lake City; New York State Department of Health (S.T.), Albany; Department of Neurology (Y.S.V.), University of South Carolina, Columbia; RTI International (N.W.), Research Triangle Park, NC; and Department of Neurology (N.E.J.), Virginia Commonwealth University, Richmond.
ORCID: 0000-0002-8328-1551

Suzanne W McDermott (SW)

From the Paul & Sheila Wellstone Muscular Dystrophy Center (P.B.K.), Department of Neurology, and Institute for Translational Neuroscience, University of Minnesota, Minneapolis; Department of Pediatrics (M.J.-F., Y.M.), University of Florida College of Medicine, Gainesville; Department of Epidemiology and Biostatistics (W.Z.), University of South Carolina, Columbia; Department of Environmental, Occupational, and Geospatial Health Sciences (S.W.M.), Graduate School of Public Health and Health Policy, City University of New York; Division of Population Health Surveillance (R.B., C.W.), Bureau of Maternal and Child Health, South Carolina Department of Health and Environmental Control, Columbia; Department of Human and Molecular Genetics (C.C.), Virginia Commonwealth University, Richmond; Department of Pediatrics (K.N.W.), University of Utah, Salt Lake City; New York State Department of Health (S.T.), Albany; Department of Neurology (Y.S.V.), University of South Carolina, Columbia; RTI International (N.W.), Research Triangle Park, NC; and Department of Neurology (N.E.J.), Virginia Commonwealth University, Richmond.
ORCID: 0000-0003-1517-5033

Reba Berry (R)

From the Paul & Sheila Wellstone Muscular Dystrophy Center (P.B.K.), Department of Neurology, and Institute for Translational Neuroscience, University of Minnesota, Minneapolis; Department of Pediatrics (M.J.-F., Y.M.), University of Florida College of Medicine, Gainesville; Department of Epidemiology and Biostatistics (W.Z.), University of South Carolina, Columbia; Department of Environmental, Occupational, and Geospatial Health Sciences (S.W.M.), Graduate School of Public Health and Health Policy, City University of New York; Division of Population Health Surveillance (R.B., C.W.), Bureau of Maternal and Child Health, South Carolina Department of Health and Environmental Control, Columbia; Department of Human and Molecular Genetics (C.C.), Virginia Commonwealth University, Richmond; Department of Pediatrics (K.N.W.), University of Utah, Salt Lake City; New York State Department of Health (S.T.), Albany; Department of Neurology (Y.S.V.), University of South Carolina, Columbia; RTI International (N.W.), Research Triangle Park, NC; and Department of Neurology (N.E.J.), Virginia Commonwealth University, Richmond.
ORCID: 0009-0003-4663-448X

Chelsea Chambers (C)

From the Paul & Sheila Wellstone Muscular Dystrophy Center (P.B.K.), Department of Neurology, and Institute for Translational Neuroscience, University of Minnesota, Minneapolis; Department of Pediatrics (M.J.-F., Y.M.), University of Florida College of Medicine, Gainesville; Department of Epidemiology and Biostatistics (W.Z.), University of South Carolina, Columbia; Department of Environmental, Occupational, and Geospatial Health Sciences (S.W.M.), Graduate School of Public Health and Health Policy, City University of New York; Division of Population Health Surveillance (R.B., C.W.), Bureau of Maternal and Child Health, South Carolina Department of Health and Environmental Control, Columbia; Department of Human and Molecular Genetics (C.C.), Virginia Commonwealth University, Richmond; Department of Pediatrics (K.N.W.), University of Utah, Salt Lake City; New York State Department of Health (S.T.), Albany; Department of Neurology (Y.S.V.), University of South Carolina, Columbia; RTI International (N.W.), Research Triangle Park, NC; and Department of Neurology (N.E.J.), Virginia Commonwealth University, Richmond.
ORCID: 0009-0005-2303-1170

Kristen N Wong (KN)

From the Paul & Sheila Wellstone Muscular Dystrophy Center (P.B.K.), Department of Neurology, and Institute for Translational Neuroscience, University of Minnesota, Minneapolis; Department of Pediatrics (M.J.-F., Y.M.), University of Florida College of Medicine, Gainesville; Department of Epidemiology and Biostatistics (W.Z.), University of South Carolina, Columbia; Department of Environmental, Occupational, and Geospatial Health Sciences (S.W.M.), Graduate School of Public Health and Health Policy, City University of New York; Division of Population Health Surveillance (R.B., C.W.), Bureau of Maternal and Child Health, South Carolina Department of Health and Environmental Control, Columbia; Department of Human and Molecular Genetics (C.C.), Virginia Commonwealth University, Richmond; Department of Pediatrics (K.N.W.), University of Utah, Salt Lake City; New York State Department of Health (S.T.), Albany; Department of Neurology (Y.S.V.), University of South Carolina, Columbia; RTI International (N.W.), Research Triangle Park, NC; and Department of Neurology (N.E.J.), Virginia Commonwealth University, Richmond.
ORCID: 0009-0009-9517-9499

Yara Mohamed (Y)

From the Paul & Sheila Wellstone Muscular Dystrophy Center (P.B.K.), Department of Neurology, and Institute for Translational Neuroscience, University of Minnesota, Minneapolis; Department of Pediatrics (M.J.-F., Y.M.), University of Florida College of Medicine, Gainesville; Department of Epidemiology and Biostatistics (W.Z.), University of South Carolina, Columbia; Department of Environmental, Occupational, and Geospatial Health Sciences (S.W.M.), Graduate School of Public Health and Health Policy, City University of New York; Division of Population Health Surveillance (R.B., C.W.), Bureau of Maternal and Child Health, South Carolina Department of Health and Environmental Control, Columbia; Department of Human and Molecular Genetics (C.C.), Virginia Commonwealth University, Richmond; Department of Pediatrics (K.N.W.), University of Utah, Salt Lake City; New York State Department of Health (S.T.), Albany; Department of Neurology (Y.S.V.), University of South Carolina, Columbia; RTI International (N.W.), Research Triangle Park, NC; and Department of Neurology (N.E.J.), Virginia Commonwealth University, Richmond.
ORCID: 0009-0005-3835-9443

Shiny Thomas (S)

From the Paul & Sheila Wellstone Muscular Dystrophy Center (P.B.K.), Department of Neurology, and Institute for Translational Neuroscience, University of Minnesota, Minneapolis; Department of Pediatrics (M.J.-F., Y.M.), University of Florida College of Medicine, Gainesville; Department of Epidemiology and Biostatistics (W.Z.), University of South Carolina, Columbia; Department of Environmental, Occupational, and Geospatial Health Sciences (S.W.M.), Graduate School of Public Health and Health Policy, City University of New York; Division of Population Health Surveillance (R.B., C.W.), Bureau of Maternal and Child Health, South Carolina Department of Health and Environmental Control, Columbia; Department of Human and Molecular Genetics (C.C.), Virginia Commonwealth University, Richmond; Department of Pediatrics (K.N.W.), University of Utah, Salt Lake City; New York State Department of Health (S.T.), Albany; Department of Neurology (Y.S.V.), University of South Carolina, Columbia; RTI International (N.W.), Research Triangle Park, NC; and Department of Neurology (N.E.J.), Virginia Commonwealth University, Richmond.
ORCID: 0000-0003-3099-4520

Y Swamy Venkatesh (YS)

From the Paul & Sheila Wellstone Muscular Dystrophy Center (P.B.K.), Department of Neurology, and Institute for Translational Neuroscience, University of Minnesota, Minneapolis; Department of Pediatrics (M.J.-F., Y.M.), University of Florida College of Medicine, Gainesville; Department of Epidemiology and Biostatistics (W.Z.), University of South Carolina, Columbia; Department of Environmental, Occupational, and Geospatial Health Sciences (S.W.M.), Graduate School of Public Health and Health Policy, City University of New York; Division of Population Health Surveillance (R.B., C.W.), Bureau of Maternal and Child Health, South Carolina Department of Health and Environmental Control, Columbia; Department of Human and Molecular Genetics (C.C.), Virginia Commonwealth University, Richmond; Department of Pediatrics (K.N.W.), University of Utah, Salt Lake City; New York State Department of Health (S.T.), Albany; Department of Neurology (Y.S.V.), University of South Carolina, Columbia; RTI International (N.W.), Research Triangle Park, NC; and Department of Neurology (N.E.J.), Virginia Commonwealth University, Richmond.
ORCID: 0009-0007-7311-4905

Christina Westfield (C)

From the Paul & Sheila Wellstone Muscular Dystrophy Center (P.B.K.), Department of Neurology, and Institute for Translational Neuroscience, University of Minnesota, Minneapolis; Department of Pediatrics (M.J.-F., Y.M.), University of Florida College of Medicine, Gainesville; Department of Epidemiology and Biostatistics (W.Z.), University of South Carolina, Columbia; Department of Environmental, Occupational, and Geospatial Health Sciences (S.W.M.), Graduate School of Public Health and Health Policy, City University of New York; Division of Population Health Surveillance (R.B., C.W.), Bureau of Maternal and Child Health, South Carolina Department of Health and Environmental Control, Columbia; Department of Human and Molecular Genetics (C.C.), Virginia Commonwealth University, Richmond; Department of Pediatrics (K.N.W.), University of Utah, Salt Lake City; New York State Department of Health (S.T.), Albany; Department of Neurology (Y.S.V.), University of South Carolina, Columbia; RTI International (N.W.), Research Triangle Park, NC; and Department of Neurology (N.E.J.), Virginia Commonwealth University, Richmond.

Nedra Whitehead (N)

From the Paul & Sheila Wellstone Muscular Dystrophy Center (P.B.K.), Department of Neurology, and Institute for Translational Neuroscience, University of Minnesota, Minneapolis; Department of Pediatrics (M.J.-F., Y.M.), University of Florida College of Medicine, Gainesville; Department of Epidemiology and Biostatistics (W.Z.), University of South Carolina, Columbia; Department of Environmental, Occupational, and Geospatial Health Sciences (S.W.M.), Graduate School of Public Health and Health Policy, City University of New York; Division of Population Health Surveillance (R.B., C.W.), Bureau of Maternal and Child Health, South Carolina Department of Health and Environmental Control, Columbia; Department of Human and Molecular Genetics (C.C.), Virginia Commonwealth University, Richmond; Department of Pediatrics (K.N.W.), University of Utah, Salt Lake City; New York State Department of Health (S.T.), Albany; Department of Neurology (Y.S.V.), University of South Carolina, Columbia; RTI International (N.W.), Research Triangle Park, NC; and Department of Neurology (N.E.J.), Virginia Commonwealth University, Richmond.
ORCID: 0000-0002-2908-3503

Nicholas E Johnson (NE)

From the Paul & Sheila Wellstone Muscular Dystrophy Center (P.B.K.), Department of Neurology, and Institute for Translational Neuroscience, University of Minnesota, Minneapolis; Department of Pediatrics (M.J.-F., Y.M.), University of Florida College of Medicine, Gainesville; Department of Epidemiology and Biostatistics (W.Z.), University of South Carolina, Columbia; Department of Environmental, Occupational, and Geospatial Health Sciences (S.W.M.), Graduate School of Public Health and Health Policy, City University of New York; Division of Population Health Surveillance (R.B., C.W.), Bureau of Maternal and Child Health, South Carolina Department of Health and Environmental Control, Columbia; Department of Human and Molecular Genetics (C.C.), Virginia Commonwealth University, Richmond; Department of Pediatrics (K.N.W.), University of Utah, Salt Lake City; New York State Department of Health (S.T.), Albany; Department of Neurology (Y.S.V.), University of South Carolina, Columbia; RTI International (N.W.), Research Triangle Park, NC; and Department of Neurology (N.E.J.), Virginia Commonwealth University, Richmond.
ORCID: 0000-0002-3917-4257

Classifications MeSH