Simultaneous measurement of the size and methylation of chromosome 4qA-D4Z4 repeats in facioscapulohumeral muscular dystrophy by long-read sequencing
説明
<jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant muscular disorder characterized by asymmetric muscle wasting and weakness. FSHD can be subdivided into two types: FSHD1, caused by contraction of the D4Z4 repeat on chromosome 4q35, and FSHD2, caused by mild contraction of the D4Z4 repeat plus aberrant hypomethylation mediated by genetic variants in <jats:italic>SMCHD1</jats:italic>, <jats:italic>DNMT3B</jats:italic>, or <jats:italic>LRIF1</jats:italic>. Genetic diagnosis of FSHD is challenging because of the complex procedures required.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>We applied Nanopore CRISPR/Cas9-targeted resequencing for the diagnosis of FSHD by simultaneous detection of D4Z4 repeat length and methylation status at nucleotide level in genetically-confirmed and suspected patients.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>We found significant hypomethylation of contracted 4q-D4Z4 repeats in FSHD1, and both 4q- and 10q-D4Z4 repeats in FSHD2. We also found that the hypomethylation in the contracted D4Z4 in FSHD1 is moderately correlated with patient phenotypes.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Our method contributes to the development for the diagnosis of FSHD using Nanopore long-read sequencing. This finding might give insight into the mechanisms by which repeat contraction causes disease pathogenesis.</jats:p> </jats:sec>
収録刊行物
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- Journal of Translational Medicine
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Journal of Translational Medicine 20 (1), 2022-11-08
Springer Science and Business Media LLC