Associated disorders

The FHL1 gene is associated with X-linked Emery-Dreifuss muscular dystrophy type 6 (EDMD6) (MedGen UID: 395525), reducing body myopathies (RBM) (MedGen UIDs: 394710, 394714) and hypertrophic cardiomyopathy (PMID: 24114807). Other FHL1-related conditions have been reported (OMIM: 300163).

Pathogenic variants in FHL1 cause approximately 10% of X-linked Emery-Dreifuss muscular dystrophy (EDMD) cases, which may present with cardiac symptoms including conduction defects, arrhythmias, and hypertrophic cardiomyopathy. FHL1 is the only known cause of reducing body myopathy and may cause as much as 3% of myofibrillar myopathy.

FHL1 encodes the four and a half LIM domains-1 protein. The LIM motif is characterized by the presence of two tandemly arranged zinc fingers. FHL1 is located in the sarcolemma, sarcomere, and nucleus. FHL1 is involved with myosin filament formation and sarcomere assembly.

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
FHL1 NM_001449.4, NM_001159702.2