2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Identification and accurate sizing of D4Z4 repeat units in patients suspected of facioscapulohumeral muscular dystrophy (FSHD) using optical genome mapping.

Identification and accurate sizing of D4Z4 repeat units in patients suspected of facioscapulohumeral muscular dystrophy (FSHD) using optical genome mapping.

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The study evaluates the use of whole genome optical mapping as an alternative method for the diagnosis of Facioscapulohumeral Muscular Dystrophy (FSHD) type 1. Currently, Southern blot is the gold standard method for FSHD diagnosis, but it is time-consuming and requires a large quantity of high-quality DNA. The researchers compared optical genome mapping (OGM) to Southern blotting and found that OGM is less time-consuming and provides a more accurate estimate of the number of D4Z4 units, the key genetic component associated with FSHD. In addition, OGM can identify mosaic cases, bi-allelic contractions, and homozygous contractions of the D4Z4 allele.<br /><br />The researchers combined OGM with next-generation sequencing (NGS) to accurately diagnose FSHD type 1 and FSHD type 2. They used OGM to identify FSHD haplotype and D4Z4 repeat number, and NGS to identify sequence and copy number variants in the SMCHD1 gene, which is associated with FSHD type 2. This combined approach was found to be practical and cost-effective.<br /><br />In their study, the researchers performed FSHD testing using OGM on 547 patients suspected of FSHD. They found that 308 of these patients had a D4Z4 contraction resulting in a diagnosis of FSHD type 1. They also performed additional testing on 252 of these patients to identify variants in the SMCHD1 gene, resulting in the identification of 10 patients with FSHD type 2. They also identified cases with mosaic alleles, cis duplications, biallelic contractions, and homozygous contractions.<br /><br />Overall, the study demonstrates that OGM combined with NGS is a viable alternative to Southern blotting for the diagnosis of FSHD. It provides a quicker and more accurate diagnosis, as well as the ability to identify different genetic variants associated with FSHD type 2.

Asset Subtitle

Presenting Author - Naga M. Guruju, PhD, FACMG; Co-Author - Vanessa Jump, BS; Co-Author - Babi Nallamilli, PhD, FACMG; Co-Author - Ruby Liu, PhD, CGC; Co-Author - Zhiwen Luo, BS; Co-Author - Madhuri Hegde, PhD;

Meta Tag

Bioinformatics

Clinical Applications of Molecular Cytogenetics

Clinical Cytogenetics

Gene Mapping

Genomic Methodologies

Imprinting

Methylation

Phenotype

Co-Author Vanessa Jump, BS

Co-Author Babi Nallamilli, PhD, FACMG

Co-Author Ruby Liu, PhD, CGC

Co-Author Zhiwen Luo, BS

Co-Author Madhuri Hegde, PhD

Presenting Author Naga M. Guruju, PhD, FACMG

Keywords

whole genome optical mapping

diagnosis

Facioscapulohumeral Muscular Dystrophy

FSHD type 1

Southern blot

OGM

D4Z4 units

mosaic cases

bi-allelic contractions