| Autor: |
Payam, Mohassel, Ning, Chang, Kaoru, Inoue, Angela, Delaney, Ying, Hu, Sandra, Donkervoort, Dimah, Saade, B Jeanne, Billioux, Brooke, Meader, Rita, Volochayev, Chamindra G, Konersman, Angela M, Kaindl, Chie-Hee, Cho, Bianca, Russell, Adrian, Rodriguez, K Wade, Foster, A Reghan, Foley, Steven A, Moore, Peter L, Jones, Carsten G, Bonnemann, Takako, Jones, Natalie D, Shaw |
| Rok vydání: |
2021 |
| Předmět: |
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| Zdroj: |
Neurology |
| ISSN: |
1526-632X |
| Popis: |
BACKGROUND AND OBJECTIVES: Facioscapulohumeral muscular dystrophy type 2 (FSHD2) and arhinia are 2 distinct disorders caused by pathogenic variants in the same gene: SMCHD1. The mechanism underlying this phenotypic divergence remains unclear. In this study, we characterize the neuromuscular phenotype of individuals with arhinia caused by SMCHD1 variants and analyze their complex genetic and epigenetic criteria to assess their risk for FSHD2. METHODS: Eleven individuals with congenital nasal anomalies, including arhinia, nasal hypoplasia, or anosmia, underwent a neuromuscular examination, genetic testing, muscle ultrasound, and muscle MRI. Risk for FSHD2 was determined by combined genetic and epigenetic analysis of 4q35 haplotype, D4Z4 repeat length, and methylation profile. We also compared expression levels of pathogenic DUX4 mRNA in primary myoblasts or dermal fibroblasts (upon myogenic differentiation or epigenetic transdifferentiation, respectively) in these individuals vs those with confirmed FSHD2. RESULTS: Among the 11 individuals with rare, pathogenic, heterozygous missense variants in exons 3–11 of SMCHD1, only a subset (n = 3/11; 1 male, 2 female; age 25–51 years) met the strict genetic and epigenetic criteria for FSHD2 (D4Z4 repeat unit length |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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