Pathogenic XPO1 variants cause a dominant neurodevelopmental disorder.

Purpose: XPO1 functions in key cellular processes, including nucleo-cytoplasmic export and mitosis. The gene is deleted in a subset of patients with the 2p15p16.1 microdeletion syndrome, however no monogenic XPO1-related disorder has been described to date.

Project GIVE: using a virtual genetics service platform to reduce health inequities and improve access to genomic care in an underserved region of Texas.

Background: The utilization of genomic information to improve health outcomes is progressively becoming more common in clinical practice. Nonetheless, disparities persist in accessing genetic services among ethnic minorities, individuals with low socioeconomic status, and other vulnerable populations. The Rio Grande Valley (RGV) at the Texas-Mexico border is predominantly Hispanic/Latino with a high poverty rate and very limited access to genetic services.

LARP1 haploinsufficiency is associated with an autosomal dominant neurodevelopmental disorder.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder (NDD) that affects approximately 4% of males and 1% of females in the United States. While causes of ASD are multi-factorial, single rare genetic variants contribute to around 20% of cases. Here, we report a case series of seven unrelated probands (6 males, 1 female) with ASD or another variable NDD phenotype attributed to de novo heterozygous loss of function or missense variants in the gene LARP1 (La ribonucleoprotein 1).

Recurrent carotid paragangliomas in a syndromic patient with a heterozygous missense variant in DNA Methyltransferase 3 Alpha.

We report a 40-year-old African American female with a novel variant in exon 8 of DNA methyltransferase 3 alpha (DNMT3A), (NM_022552.4: c.905G>C, p.

Improving access to exome sequencing in a medically underserved population through the Texome Project.

Purpose: Genomic medicine can end diagnostic odysseys for patients with complex phenotypes; however, limitations in insurance coverage and other systemic barriers preclude individuals from accessing comprehensive genetics evaluation and testing.

Methods: The Texome Project is a 4-year study that reduces barriers to genomic testing for individuals from underserved and underrepresented populations. Participants with undiagnosed, rare diseases who have financial barriers to obtaining exome sequencing (ES) clinically are enrolled in the Texome Project.

Families' experiences accessing care after genomic sequencing in the pediatric cancer context: "It's just been a big juggle".

Access to genomic sequencing (GS) and resulting recommendations have not been well described in pediatric oncology. GS results may provide a cancer predisposition syndrome (CPS) diagnosis that warrants screening and specialist visits beyond cancer treatment, including testing or surveillance for family members. The Texas KidsCanSeq (KCS) Study evaluated implementation of GS in a diverse pediatric oncology population.

Reducing Time to Diagnosis of Rare Genetic Diseases in a Medically Underserved Hispanic Population- Lessons Learned for Meaningful Engagement.

Background: The utilization of genomic information to improve health outcomes is progressively becoming more common in clinical practice. Nonetheless, disparities persist in accessing genetic services among ethnic minorities, individuals with low socioeconomic status, and other vulnerable populations. The Rio Grande Valley at the Texas-Mexico border is predominantly Hispanic with a high poverty rate and an increased prevalence of birth defects, with very limited access to genetics services.

Precision therapy for a medically actionable ATP1A3 variant from a genomic medicine program in an underserved population.

Background: Genomic medicine is revolutionizing the diagnosis of rare diseases, but the implementation has not benefited underrepresented populations to the same degree. Here, we report the case of a 7-year-old boy with hypotonia, global developmental delay, strabismus, seizures, and previously suspected mitochondrial myopathy. This proband comes from an underrepresented minority and was denied exome sequencing by his public insurance.

Unwind and Relax: DDX3X RNA Helicase as a Critical Mediator of Cortical Neurogenesis.

In this issue of Neuron, Lennox et al. (2020) report the largest cohort of patients to date with DDX3X syndrome, discovering unique genotype-phenotype relationships that inform molecular pathogenesis. They then uncover unique roles of DDX3X in cortical neuron development and ribonucleoprotein granule formation.

Transmitter release site organization can predict synaptic function at the neuromuscular junction.

We have investigated the impact of transmitter release site (active zone; AZ) structure on synaptic function by physically rearranging the individual AZ elements in a previously published frog neuromuscular junction (NMJ) AZ model into the organization observed in a mouse NMJ AZ. We have used this strategy, purposefully without changing the properties of AZ elements between frog and mouse models (even though there are undoubtedly differences between frog and mouse AZ elements in vivo), to directly test how structure influences function at the level of an AZ. Despite a similarly ordered ion channel array substructure within both frog and mouse AZs, frog AZs are much longer and position docked vesicles in a different location relative to AZ ion channels.