CLIA Laboratory Testing for Facioscapulohumeral Dystrophy: A Retrospective Analysis

Autumn Rieken; Aaron D Bossler; Katherine D Mathews; Steven A Moore

doi:10.1212/WNL.0000000000011412

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CLIA Laboratory Testing for Facioscapulohumeral Dystrophy: A Retrospective Analysis

Journal article

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CLIA Laboratory Testing for Facioscapulohumeral Dystrophy: A Retrospective Analysis

Autumn Rieken, Aaron D Bossler, Katherine D Mathews and Steven A Moore

Neurology, Vol.96(7), pp.e1054-e1062

02/16/2021

DOI: 10.1212/WNL.0000000000011412

PMCID: PMC8055331

PMID: 33443126

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Abstract

To summarize facioscapulohumeral muscular dystrophy (FSHD) diagnostic testing results from the University of Iowa Molecular Pathology Laboratory. All FSHD tests performed in the diagnostic laboratory from January 2015 to July 2019 were retrospectively reviewed. Testing was by restriction enzyme digestion and Southern blot analysis with sequencing of , if indicated. Cases were classified as FSHD1 (4q35 EcoRI size ≤40 kb; 1-10 D4Z4 repeats), FSHD2 (permissive 4q35A allele, D4Z4 hypomethylation, and pathogenic variant), or non-FSHD1,2. We also noted cases with borderline EcoRI fragment size (41-43 kb; 11 D4Z4 repeats), cases that meet criteria for both FSHD1 and FSHD2, somatic mosaicism, and cases with hybrid alleles that add complexity to test interpretation. Of the 1,594 patients with FSHD tests included in the analysis, 703 (44.1%) were diagnosed with FSHD. Among these positive tests, 664 (94.5%) met criteria for FSHD1 and 39 (5.5%) met criteria for FSHD2. Of all 1,594 cases, 20 (1.3%) had a 4q35 allele of borderline size, 23 (1.5%) were somatic mosaics, and 328 (20.9%) had undergone translocation events. Considering only cases with at least 1 4q35A allele, D4Z4 repeat number differed significantly among groups: FSHD1 cases median 6.0 (interquartile range [IQR] 4-7) repeats, FSHD2 cases 15.0 (IQR 12-22) repeats, and non-FSHD1,2 cases 28.0 (IQR 19-40) repeats. FSHD1 accounts for 94.5% of genetically confirmed cases of FSHD. The data show a continuum of D4Z4 repeat numbers with FSHD1 samples having the fewest, FSHD2 an intermediate number, and non-FSHD1,2 the most.

Diagnostic Tests, Routine

DNA Methylation

Phenotype

Muscular Dystrophy, Facioscapulohumeral - diagnosis

Humans

Alleles

Muscular Dystrophy, Facioscapulohumeral - genetics

Mutation

Pathology, Molecular

Chromosomal Proteins, Non-Histone - genetics

Details

Title: Subtitle: CLIA Laboratory Testing for Facioscapulohumeral Dystrophy: A Retrospective Analysis
Creators: Autumn Rieken - From the Departments of Pathology (A.R., A.D.B., S.A.M.) and Pediatrics and Neurology (A.R., K.D.M.), Carver College of Medicine, The University of Iowa, Iowa City
Aaron D Bossler - From the Departments of Pathology (A.R., A.D.B., S.A.M.) and Pediatrics and Neurology (A.R., K.D.M.), Carver College of Medicine, The University of Iowa, Iowa City
Katherine D Mathews - From the Departments of Pathology (A.R., A.D.B., S.A.M.) and Pediatrics and Neurology (A.R., K.D.M.), Carver College of Medicine, The University of Iowa, Iowa City
Steven A Moore - From the Departments of Pathology (A.R., A.D.B., S.A.M.) and Pediatrics and Neurology (A.R., K.D.M.), Carver College of Medicine, The University of Iowa, Iowa City. steven-moore@uiowa.edu
Resource Type: Journal article
Publication Details: Neurology, Vol.96(7), pp.e1054-e1062
DOI: 10.1212/WNL.0000000000011412
PMID: 33443126
PMCID: PMC8055331
NLM abbreviation: Neurology
ISSN: 0028-3878
eISSN: 1526-632X
Publisher: United States
Grant note: P50 NS053672 / NINDS NIH HHS U54 NS053672 / NINDS NIH HHS
Language: English
Date published: 02/16/2021
Academic Unit: Neurology; Stead Family Department of Pediatrics; Pathology; Iowa Neuroscience Institute; Neurology (Pediatrics)
Record Identifier: 9984070841102771

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