Hypomethylation of contracted D4Z4 repeats in facioscapulohumeral muscular dystrophy
Hiramuki, Y.; Kure, Y.; Saito, Y.; Ogawa, M.; Ishikawa, K.; Mori-Yoshimura, M.; Oya, Y.; Takahashi, Y.; Kim, D.-S.; Arai, N.; Mori, C.; Matsumura, T.; Hamano, T.; Nakamura, K.; Ikezoe, K.; Hayashi, S.; Goto, Y.; Noguchi, S.; Nishino, I.
Show abstract
Facioscapulohumeral muscular dystrophy (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 SMCHD1, DNMT3B, or LRIF1. Genetic diagnosis of FSHD is challenging because of the complex procedures required. Here, 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. We found significant hypomethylation of contracted D4Z4 repeats in FSHD1 and strong correlation between methylation rate and patient phenotype. This finding can explain how repeat contraction contributes to disease pathogenesis by activating DUX4 expression.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Using single molecule Molecular Inversion Probes as a cost-effective, high-throughput sequencing approach to target all genes and loci associated with macular diseases 92%
- Phasing of de novo mutations using a scaled-up multiple amplicon long-read sequencing approach 91%
- Generation and mutational analysis of a transgenic mouse model of human SRY 91%
Similar papers in this journal
- Resolving the diagnostic odyssey in inherited retinal dystrophies through long-read genome sequencing 92%
- Next-generation phenotyping in Nigerian children with Cornelia de Lange Syndrome 90%
- Known pathogenic gene variants and new candidates detected in Sudden Unexpected Infant Death using Whole Genome Sequencing 89%
Similar papers in this journal
- Structural variant calling and clinical interpretation in 6224 unsolved rare disease exomes 91%
- A genome-wide association analysis of loss of ambulation in dystrophinopathy patients suggests multiple candidate modifiers of disease severity 90%
- Variable Number Tandem Repeats (VNTRs) as modifiers of breast cancer risk in carriers of BRCA1 185delAG 89%
Similar papers in this journal
Similar papers in this journal
- Evaluation of optical genome mapping in clinical genetic testing of facioscapulohumeral muscular dystrophy 94%
- Array Comparative Genomic Hybridisation and Droplet Digital PCR uncover recurrent copy number variation of the titin segmental duplication region 91%
- VarGenius-HZD allows accurate detection of rare homozygous or hemizygous deletions in targeted sequencing leveraging breadth of coverage 91%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.