Expression of LIM domain-binding 3 (LDB3), a striated muscle Z-band alternatively spliced PDZ-motif protein in the nervous system.

LIM domain-binding 3 (LDB3) is a member of the Enigma family of PDZ-LIM proteins. LDB3 has been reported as a striated muscle-specific Z-band alternatively spliced protein that plays an important role in mechanosensory actin cytoskeleton remodeling. This study shows that LDB3 is broadly expressed in the central and peripheral nervous system of human and mouse.

Simple and economical HandClench Relaxometer device for reliable and sensitive measurement of grip myotonia in myotonic dystrophy.

Grip myotonia and weakness are attractive treatment response biomarkers in clinical trials of myotonic dystrophy type 1 (DM1). There is a need to develop simple, patient-friendly and reproducible methods of quantifying grip myotonia in multisite trial settings. We designed a HandClench Relaxometer (HCR) that measures grip myotonia and strength.

Brief assessment of cognitive function in myotonic dystrophy: Multicenter longitudinal study using computer-assisted evaluation.

Introduction/aims: Myotonic dystrophy type 1 (DM1) is known to affect cognitive function, but the best methods to assess central nervous system involvement in multicenter studies have not been determined. In this study our primary aim was to evaluate the potential of computerized cognitive tests to assess cognition in DM1.

Methods: We conducted a prospective, longitudinal, observational study of 113 adults with DM1 at six sites.

Improving the efficacy of exome sequencing at a quaternary care referral centre: novel mutations, clinical presentations and diagnostic challenges in rare neurogenetic diseases.

Background: We used a multimodal approach including detailed phenotyping, whole exome sequencing (WES) and candidate gene filters to diagnose rare neurological diseases in individuals referred by tertiary neurology centres.

Methods: WES was performed on 66 individuals with neurogenetic diseases using candidate gene filters and stringent algorithms for assessing sequence variants. Pathogenic or likely pathogenic missense variants were interpreted using in silico prediction tools, family segregation analysis, previous publications of disease association and relevant biological assays.

Myopathy associated LDB3 mutation causes Z-disc disassembly and protein aggregation through PKCα and TSC2-mTOR downregulation.

Mechanical stress induced by contractions constantly threatens the integrity of muscle Z-disc, a crucial force-bearing structure in striated muscle. The PDZ-LIM proteins have been proposed to function as adaptors in transducing mechanical signals to preserve the Z-disc structure, however the underlying mechanisms remain poorly understood. Here, we show that LDB3, a well-characterized striated muscle PDZ-LIM protein, modulates mechanical stress signaling through interactions with the mechanosensing domain in filamin C, its chaperone HSPA8, and PKCα in the Z-disc of skeletal muscle.