WGS and RNA Studies Diagnose Noncoding Variants in Males With High Creatine Kinase.

Objective: To describe the diagnostic utility of whole-genome sequencing and RNA studies in boys with suspected dystrophinopathy, for whom multiplex ligation-dependent probe amplification and exomic parallel sequencing failed to yield a genetic diagnosis, and to use remnant normal splicing in 3 families to define critical levels of wild-type dystrophin bridging clinical spectrums of Duchenne to myalgia.

Methods: Exome, genome, and/or muscle RNA sequencing was performed for 7 males with elevated creatine kinase. PCR of muscle-derived complementary DNA (cDNA) studied consequences for premessenger RNA (pre-mRNA) splicing.

Targeted gene panel use in 2249 neuromuscular patients: the Australasian referral center experience.

Objective: To develop, test, and iterate a comprehensive neuromuscular targeted gene panel in a national referral center.

Methods: We designed two iterations of a comprehensive targeted gene panel for neuromuscular disorders. Version 1 included 336 genes, which was increased to 464 genes in Version 2.

Anxiety and depression in a sample of UK college students: a study of prevalence, comorbidity, and quality of life.

This study sought to estimate the prevalence of depression and anxiety in UK college students and examine associations between mental health symptoms and quality of life (QoL). Associations between psychiatric comorbidity and degree of QoL impairment were also investigated. Participants ( = 286) were recruited from a UK university (76.

Recessive MYH7-related myopathy in two families.

Myopathies due to recessive MYH7 mutations are exceedingly rare, reported in only two families to date. We describe three patients from two families (from Australia and the UK) with a myopathy caused by recessive mutations in MYH7. The Australian family was homozygous for a c.

A mutation in MT-TW causes a tRNA processing defect and reduced mitochondrial function in a family with Leigh syndrome.

Leigh syndrome (LS) is a progressive mitochondrial neurodegenerative disorder, whose symptoms most commonly include psychomotor delay with regression, lactic acidosis and a failure to thrive. Here we describe three siblings with LS, but with additional manifestations including hypertrophic cardiomyopathy, hepatosplenomegaly, cholestatic hepatitis, and seizures. All three affected siblings were found to be homoplasmic for an m.

Quantifying the Effects of Predator and Prey Body Size on Sea Star Feeding Behaviors.

Body size plays a crucial role in determining the strength of species interactions, population dynamics, and community structure. We measured how changes in body size affect the trophic relationship between the sea star Pisaster ochraceus and its prey, the mussel Mytilus trossulus. We tested the effects of a wide range of predator and prey sizes on sea stars' prey-size preference, feeding rate, and prey tissue consumption.

Complex sarcolemmal invaginations mimicking myotendinous junctions in a case of Laing early-onset distal myopathy.

Distal myopathies are a group of clinically and pathologically overlapping muscle diseases that are genetically complex and can represent a diagnostic challenge. Laing early-onset distal myopathy (MPD1) is a form of distal myopathy caused by mutations in the MYH7 gene, which encodes the beta myosin heavy chain protein expressed in type 1 skeletal muscle fibers and cardiac myocytes. Here, we present a case of genetically confirmed MPD1 with a typical clinical presentation but distinctive light microscopic and ultrastructural findings on muscle biopsy.

Mutations of GPR126 are responsible for severe arthrogryposis multiplex congenita.

Arthrogryposis multiplex congenita is defined by the presence of contractures across two or more major joints and results from reduced or absent fetal movement. Here, we present three consanguineous families affected by lethal arthrogryposis multiplex congenita. By whole-exome or targeted exome sequencing, it was shown that the probands each harbored a different homozygous mutation (one missense, one nonsense, and one frameshift mutation) in GPR126.

Novel mutations widen the phenotypic spectrum of slow skeletal/β-cardiac myosin (MYH7) distal myopathy.

Laing early onset distal myopathy and myosin storage myopathy are caused by mutations of slow skeletal/β-cardiac myosin heavy chain encoded by the gene MYH7, as is a common form of familial hypertrophic/dilated cardiomyopathy. The mechanisms by which different phenotypes are produced by mutations in MYH7, even in the same region of the gene, are not known. To explore the clinical spectrum and pathobiology, we screened the MYH7 gene in 88 patients from 21 previously unpublished families presenting with distal or generalized skeletal muscle weakness, with or without cardiac involvement.

Elevated water temperature and carbon dioxide concentration increase the growth of a keystone echinoderm.

Anthropogenic climate change poses a serious threat to biodiversity. In marine environments, multiple climate variables, including temperature and CO(2) concentration ([CO(2)]), are changing simultaneously. Although temperature has well-documented ecological effects, and many heavily calcified marine organisms experience reduced growth with increased [CO(2)], little is known about the combined effects of temperature and [CO(2)], particularly on species that are less dependent on calcified shells or skeletons.

[Congenital cataracts facial dysmorphism neuropathy syndrome--first Hungarian case report].

The congenital cataracts facial dysmorphism neuropathy (CCFDN) syndrome (OMIM 604168) is a recently described autosomal recessive developmental disorder. It is almost completely restricted to an endogamous group of the European Vlax Roma population, called the Rudari. The CCFDN syndrome is a complex phenotype involving multiple systems, characterized by facial dysmorphism, congenital cataracts, microcorneae, delayed early motor and intellectual development, hypogonadotrop hypogonadism, hypomyelination of the peripheral nervous system, and serious complications related to general anaesthesia.

Congenital cataracts facial dysmorphism neuropathy (CCFDN) syndrome: a rare cause of parainfectious rhabdomyolysis.

Congenital cataracts-facial dysmorphism-neuropathy syndrome (CCFDN, MIM: 604168), is a recently delineated neurogenetic disease causing recurrent episodes of rhabdomyolysis; prevention and early diagnosis of rhabdomyolysis should be part of the clinical management of the disease.

Clinical spectrum of CMT4C disease in patients homozygous for the p.Arg1109X mutation in SH3TC2.

We investigated the manifestations of CMT4C disease in a genetically homogeneous group of patients homozygous for the recently identified Gypsy founder mutation p.Arg1109X in SH3TC2. We observed a surprising degree of variation in age at onset, rate of progression, extent and severity of motor and sensory involvement, scoliosis, and cranial nerve involvement, suggesting that the phenotypic spectrum of CMT4C disease is much broader than the classical diagnostic criteria.

Founder mutation causing infantile GM1-gangliosidosis in the Gypsy population.

The Gypsies are a trans-national founder population of Asian descent, whose genetic heritage is still incompletely characterized. Here, we describe the first founder mutation leading to a lysosomal storage disorder in this population: R59H in GLB1, which causes infantile GM1-gangliosidosis. The R59H carrier rate is approximately 2% in the general Gypsy population and approximately 10% in the Rudari sub-isolate.

Mutation history of the roma/gypsies.

The 8-10 million European Roma/Gypsies are a founder population of common origins that has subsequently split into multiple socially divergent and geographically dispersed Gypsy groups. Unlike other founder populations, whose genealogy has been extensively documented, the demographic history of the Gypsies is not fully understood and, given the lack of written records, has to be inferred from current genetic data. In this study, we have used five disease loci harboring private Gypsy mutations to examine some missing historical parameters and current structure.

Ocular features of the congenital cataracts facial dysmorphism neuropathy syndrome.

Objective: To determine the nature and course of ophthalmologic abnormalities in congenital cataracts facial dysmorphism neuropathy (CCFDN) syndrome in a genetically verified group of 9 patients.

Study Design: Observational case series.

Participants: Nine affected male individuals of 5 pedigrees aged 1.

Partial deficiency of the C-terminal-domain phosphatase of RNA polymerase II is associated with congenital cataracts facial dysmorphism neuropathy syndrome.

Congenital cataracts facial dysmorphism neuropathy (CCFDN) syndrome (OMIM 604168) is an autosomal recessive developmental disorder that occurs in an endogamous group of Vlax Roma (Gypsies; refs. 1-3). We previously localized the gene associated with CCFDN to 18qter, where a conserved haplotype suggested a single founder mutation.