Novel mutation in the MYH2 gene in a symptomatic neonate with a hereditary myosin myopathy

INTRODUCTION: Hereditary myosin myopathies are muscle disorders caused by mutations in myosin heavy chain genes. The MYH2 gene encodes the fast 2A skeletal muscle isoform, and mutations manifest as joint contractures, muscle weakness, and external ophthalmoplegia. Muscle biopsy shows decreased type 2A fibers, and vacuoles are sometimes present in adults with progressive disease. PRESENTATION OF CASE: This case describes a full term baby boy with hypotonia, dysmorphic features, dysphagia, and aspiration. Whole genome sequencing detected a novel heterozygous variant in the MYH2 gene. Muscle biopsy showed decreased type 2A fibers and vacuoles in myofibers. DISCUSSION: Hypotonia and dysphagia are common in infants with a MYH2 myopathy. However, dysmorphic features and vacuoles on biopsy have not previous been described in infants with MYH2 myopathies. CONCLUSION: This case reports an unusual phenotype of a rare neonatal-onset congenital myopathy associated with a novel heterozygous variant in MYH2.

Effect of dietary l-carnitine supplementation to sows during gestation and/or lactation on sow productivity, muscle maturation and lifetime growth in progeny from large litters

Genetic selection for increased sow prolificacy has resulted in decreased mean piglet birth weight. This study aimed to investigate the effect of l-carnitine (CAR) supplementation to sows during gestation and/or lactation on sow productivity, semitendinosus muscle (STM) maturity and lifetime growth in progeny. Sixty-four sows were randomly assigned to one of the four dietary treatments at breeding until weaning: CONTROL (0 mg CAR/d), GEST (125 mg CAR/d during gestation), LACT (250 mg CAR/d during lactation) and BOTH (125 mg CAR/d during gestation and 250 mg CAR/d during lactation). The total number of piglets born per litter was greater for sows supplemented with CAR during gestation (17·3 v. 15·8 (sem 0·52); P < 0·05). Piglet birth weight (total and live) was unaffected by sow treatment (P > 0·05). Total myofibre number (P = 0·08) and the expression level of selected myosin heavy chain genes in the STM (P < 0·05) were greater in piglets of sows supplemented with CAR during gestation. Pigs from sows supplemented with CAR during gestation had lighter carcasses at slaughter than pigs from non-supplemented sows during gestation (83·8 v. 86·7 (sem 0·86) kg; P < 0·05). In conclusion, CAR supplementation during gestation increased litter size at birth without compromising piglet birth weight. Results also showed that the STM of piglets born to sows supplemented with CAR during gestation was more developed at birth. However, carcass weight at slaughter was reduced in progeny of sows supplemented with CAR during gestation. The CAR supplementation strategy applied during gestation in this study could be utilised by commercial pork producers to increase sow litter size and improve offspring muscle development.

Fundamental constraints in synchronous muscle limit superfast motor control in vertebrates

Superfast muscles (SFMs) are extremely fast synchronous muscles capable of contraction rates up to 250 Hz, enabling precise motor execution at the millisecond time scale. SFM phenotypes have been discovered in most major vertebrate lineages, but it remains unknown whether all SFMs share excitation-contraction coupling pathway adaptations for speed, and if SFMs arose once, or from independent evolutionary events. Here, we demonstrate that to achieve rapid actomyosin crossbridge kinetics bat and songbird SFM express myosin heavy chain genes that are evolutionarily and ontologically distinct. Furthermore, we show that all known SFMs share multiple functional adaptations that minimize excitation-contraction coupling transduction times. Our results suggest that SFM evolved independently in sound-producing organs in ray-finned fish, birds, and mammals, and that SFM phenotypes operate at a maximum operational speed set by fundamental constraints in synchronous muscle. Consequentially, these constraints set a fundamental limit to the maximum speed of fine motor control.

Fundamental constraints in synchronous muscle limit superfast motor control in vertebrates

Superfast muscles (SFM) are extremely fast synchronous muscles capable of contraction rates up to 250 Hz, enabling precise motor execution at the millisecond time scale. To allow such speed, the archetypal SFM, found in the toadfish swimbladder, has hallmark structural and kinetic adaptations at each step of the conserved excitation-contraction coupling (ECC) pathway. More recently SFM phenotypes have been discovered in most major vertebrate lineages, but it remains unknown whether all SFM share ECC adaptations for speed, and if SFM arose once, or from independent evolutionary events. Here we use genomic analysis to identify the myosin heavy chain genes expressed in bat and songbird SFM to achieve rapid actomyosin crossbridge kinetics and demonstrate that these are evolutionarily and ontologically distinct. Furthermore, by quantifying cellular morphometry and calcium signal transduction combined with force measurements we show that all known SFM share multiple functional adaptations that minimize ECC transduction times. Our results suggest that SFM evolved independently in sound producing organs in ray-finned fish, birds, and mammals, and that SFM phenotypes operate at a maximum operational speed set by fundamental constraints in synchronous muscle. Consequentially, these constraints set a fundamental limit to the maximum speed of fine motor control.