Influential Factors for Disclosing a Tuberous Sclerosis Complex Diagnosis to Romantic Partners.

Background: Tuberous sclerosis complex (TSC) is a genetic condition characterized by multiorgan tumor predisposition. Owing to the variability, heritability, and severity of the condition, individuals with TSC may face psychosocial challenges within romantic relationships including disclosing their diagnosis to romantic partners. Despite disclosure being explored in other genetic conditions, this area has not yet been explored in the TSC community, which faces unique challenges in overall health and quality of life.

Parenting Stress in Tuberous Sclerosis Complex.

Background: Tuberous sclerosis complex (TSC) is a multisystemic genetic disorder with clinical variability. As the needs of children with TSC may differ, parenting demands may similarly differ. Characterizing parenting stress, or emotional maladaptation from parenting duties, can enable health care providers to assist parents of children with TSC.

Complete mitochondrial genome of the introduced Indian walking stick (Lonchodidae, Insecta) from California.

We present the complete mitochondrial genome of from Salinas, CA. The mitochondrial genome of is circular, AT rich (78.1%), and 16,671 bp in length.

Genetically and clinically confirmed atypical cerebrotendinous xanthomatosis with normal cholestanol and marked elevations of bile acid precursors and bile alcohols.

Background: Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive lipid disorder. Affected patients often remain undiagnosed until the age of 20-30 years, when they have already developed significant neurologic disease that may not be reversible. An elevated plasma cholestanol concentration has been accepted as a diagnostic criterion for CTX for decades.

Variants in the WDR44 WD40-repeat domain cause a spectrum of ciliopathy by impairing ciliogenesis initiation.

WDR44 prevents ciliogenesis initiation by regulating RAB11-dependent vesicle trafficking. Here, we describe male patients with missense and nonsense variants within the WD40 repeats (WDR) of WDR44, an X-linked gene product, who display ciliopathy-related developmental phenotypes that we can model in zebrafish. The patient phenotypic spectrum includes developmental delay/intellectual disability, hypotonia, distinct craniofacial features and variable presence of brain, renal, cardiac and musculoskeletal abnormalities.

mTOR Modulation of through hERG1b-Dependent Mechanisms in Lipotoxic Heart.

In the atria, the rapid delayed rectifier channel () is a critical contributor to repolarization. In lipotoxic atria, increased activity of the serine/threonine mammalian target of rapamycin (mTOR) may remodel and predispose patients to arrhythmias. To investigate whether mTOR produced defects in channel function (protein expression and gating mechanisms), electrophysiology and biochemical assays in HEK293 cells stably expressing hERG1a/1b, and adult guinea pig atrial myocytes were used.

Macrophage-Dependent Interleukin-6-Production and Inhibition of Contributes to Acquired QT Prolongation in Lipotoxic Guinea Pig Heart.

In the heart, the delayed rectifier K current, , composed of the rapid () and slow () components contributes prominently to normal cardiac repolarization. In lipotoxicity, chronic elevation of pro-inflammatory cytokines may remodel , elevating the risk for ventricular arrythmias and sudden cardiac death. We investigated whether and how the pro-inflammatory interleukin-6 altered in the heart, using electrophysiology to evaluate changes in in adult guinea pig ventricular myocytes.

Behavioral Phenotyping in a Murine Model of -Associated Parkinson Disease.

Mutations in , the gene encoding glucocerebrosidase, are common genetic risk factors for Parkinson disease (PD). While the mechanism underlying this relationship is unclear, patients with -associated PD often have an earlier onset and faster progression than idiopathic PD. Previously, we modeled -associated PD by crossing haploinsufficient mice with mice overexpressing a human mutant α-synuclein transgene (), observing an earlier demise, shorter life span and faster symptom progression, although behavioral testing was not performed.

Pro-cathepsin D, Prosaposin, and Progranulin: Lysosomal Networks in Parkinsonism.

Mutations in GBA1, the gene encoding the lysosomal hydrolase glucocerebrosidase (GCase), are a risk factor for parkinsonism. Pursuing the potential mechanisms underlying this risk in aging neurons, we propose a new network uniting three major lysosomal proteins: (i) cathepsin D (CTSD), which plays a major role in α-synuclein (SNCA) degradation and prosaposin (PSAP) cleavage; (ii) PSAP, essential for GCase activation and progranulin (PGRN) transport; and (iii) PGRN, impacting lysosomal biogenesis, PSAP trafficking, and CTSD maturation. We hypothesize that alterations to this network and associated receptors modify lysosomal function and subsequently impact both SNCA degradation and GCase activity.

Glucocerebrosidase as a therapeutic target for Parkinson's disease.

: The association between Gaucher disease, caused by the inherited deficiency of glucocerebrosidase, and Parkinson's disease was first recognized in the clinic, noting that patients with Gaucher disease and their carrier relatives had an increased incidence of Parkinson's disease. Currently, mutations in glucocerebrosidase () are the most common genetic risk factor for Parkinson's disease and dementia with Lewy bodies, with an inverse relationship between glucocerebrosidase and α-synuclein, a key factor in Parkinson pathogenesis. The hypothesis that therapeutic enhancement of brain glucocerebrosidase levels might reduce the aggregation, accumulation or spread of α-synuclein has spurred great interest in glucocerebrosidase as a novel therapeutic target.

Glucocerebrosidase and its relevance to Parkinson disease.

Mutations in GBA1, the gene encoding the lysosomal enzyme glucocerebrosidase, are among the most common known genetic risk factors for the development of Parkinson disease and related synucleinopathies. A great deal is known about GBA1, as mutations in GBA1 are causal for the rare autosomal storage disorder Gaucher disease. Over the past decades, significant progress has been made in understanding the genetics and cell biology of glucocerebrosidase.

Can GBA1-Associated Parkinson Disease Be Modeled in the Mouse?

Homozygous and heterozygous mutations in GBA1, the gene implicated in Gaucher disease, increase the risk and severity of Parkinson disease (PD). We evaluated the design, phenotype, strengths, and limitations of current GBA1-associated PD mouse models. Although faithful modeling of a genetic risk factor poses many challenges, the different approaches taken were successful in revealing predisposing abnormalities in heterozygotes for GBA1 mutations and demonstrating the deleterious effects of GBA1 impairment on the PD course in PD models.