Biallelic variants in GTF3C5, a regulator of RNA polymerase III-mediated transcription, cause a multisystem developmental disorder.

General transcription factor IIIC subunit 5 (GTF3C5) encodes transcription factor IIIC63 (TFIIIC63). It binds to DNA to recruit another transcription factor, TFIIIB, and RNA polymerase III (Pol III) to mediate the transcription of small noncoding RNAs, such as tRNAs. Here, we report four individuals from three families presenting with a multisystem developmental disorder phenotype with biallelic variants in GTF3C5.

Collaborative efforts to improve genetic testing in the neonatal intensive care unit.

Objective: To reduce unnecessary simultaneous karyotype analysis and chromosomal microarray (CMA) testing in the neonatal intensive care unit (NICU).

Study Design: This quality improvement study investigated the effect of collaborative efforts between the NICU, cytogenetics, and clinical genetics on numbers of genetic tests, rates of abnormal tests, and number of genetics consults comparing baseline and 5-month intervention periods.

Results: Simultaneous karyotype analyses and CMAs decreased due to a decrease in karyotype testing (11.

The D409H variant in GBA1: Challenges in predicting the Gaucher phenotype in the newborn screening era.

Gaucher disease (GD) is an autosomal recessive disorder resulting from glucocerebrosidase deficiency due to pathologic variants in GBA1. While clinically heterogeneous, GD encompasses three types, non-neuronopathic (GD1), acute neuronopathic (GD2), and chronic neuronopathic (GD3). Newborn screening (NBS), which has made remarkable inroads in detecting certain diseases before detrimental health consequences and fatality ensues, is now being piloted for GD in several states and countries.

Beyond Trinucleotide Repeat Expansion in Fragile X Syndrome: Rare Coding and Noncoding Variants in and Associated Phenotypes.

(FMRP translational regulator 1) variants other than repeat expansion are known to cause disease phenotypes but can be overlooked if they are not accounted for in genetic testing strategies. We collected and reanalyzed the evidence for pathogenicity of coding, noncoding, and copy number variants published to date. There is a spectrum of disease-causing variation, with clinical and functional evidence supporting pathogenicity of five splicing, five missense, one in-frame deletion, one nonsense, and four frameshift variants.

Use of dexamethasone in idiopathic, acute pediatric rhabdomyolysis.

Current rhabdomyolysis treatment guidelines vary based on the etiology and diagnosis, yet many cases evade conclusive diagnosis. In these cases, treatment options remain largely limited to fluids and supportive therapy. We present two cases of acute rhabdomyolysis diagnosed in the emergency department: a 5-year-old boy with sudden onset bilateral flank pain, and a 13-year-old boy with 2-3 days of worsening pectoral and shoulder pain.

Clinical characteristics of individual organ system disease in non-motile ciliopathies.

Non-motile ciliopathies (disorders of the primary cilia) include autosomal dominant and recessive polycystic kidney diseases, nephronophthisis, as well as multisystem disorders Joubert, Bardet-Biedl, Alström, Meckel-Gruber, oral-facial-digital syndromes, and Jeune chondrodysplasia and other skeletal ciliopathies. Chronic progressive disease of the kidneys, liver, and retina are common features in non-motile ciliopathies. Some ciliopathies also manifest neurological, skeletal, olfactory and auditory defects.

Enlarged parietal foramina: a review of genetics, prognosis, radiology, and treatment.

Introduction: Enlarged parietal foramina are variable ossification defects in the parietal bones that present as symmetric radiolucencies on skull radiographs. In contrast to the normal small parietal foramina, enlarged parietal foramina are a hereditary condition and genes associated with it have been identified.

Methods: A literature review was performed to discuss the many known findings related to enlarged parietal foramina.