Expanding the Molecular and Clinical Phenotype of Patients With De Novo Variants in KIF5C: A Six Patient Case Series.

Heterozygous de novo loss of function variants in the motor domain of KIF5C are associated with a neurodevelopmental disorder characterized by infantile-onset epilepsy, frontal cortical dysplasia, and developmental delays including motor and speech impairments. Previously, only three missense variants in KIF5C were known to be pathogenic. We identified an additional six patients with significant developmental delays with heterozygous de novo variants in the KIF5C gene (Glu237Val, Thr93Ile, Thr93Asn, Ser90del, Lys92Arg, and Glu237Lys), of which four variants have not been reported before.

TELO2-related syndrome (You-Hoover-Fong syndrome): Description of 14 new affected individuals and review of the literature.

You-Hoover-Fong syndrome (YHFS) is an autosomal recessive condition caused by pathogenic variants in the TELO2 gene. Affected individuals were reported to have global developmental delay, intellectual disability, microcephaly, dysmorphic facial features, ocular involvement including cortical visual impairment, strabismus, cataract and rotatory nystagmus, movement disorder, hypertonia and spasticity, balance disturbance and ataxia, and abnormal sleep pattern. Other features reported include poor growth, cleft palate, cardiac malformations, epilepsy, scoliosis, and hearing loss.

Interstitial deletion 4p15.32p16.1 and complex chromoplexy in a female proband with severe neurodevelopmental delay, growth failure and dysmorphism.

Complex chromosomal rearrangements involve the restructuring of genetic material within a single chromosome or across multiple chromosomes. These events can cause serious human disease by disrupting coding DNA and gene regulatory elements via deletions, duplications, and structural rearrangements. Here we describe a 5-year-old female with severe developmental delay, dysmorphic features, multi-suture craniosynostosis, and growth failure found to have a complex series of balanced intra- and inter-chromosomal rearrangements involving chromosomes 4, 11, 13, and X.

Further description of two patients with biallelic variants in NADSYN1 in association with cardiac and vertebral anomalies.

Congenital nicotinamide adenine dinucleotide (NAD) deficiency disorders are associated with pathogenic variants in the genes NADSYN1, HAAO, and KYNU. These disorders overlap with the anomalies present in vertebral, anal, cardiac, tracheoesophageal, radial and renal, and limb anomalies (VATER/VACTERL) association and often result in premature death. Children who survive typically have developmental delays or intellectual disability.

Inborn error of metabolism patients after liver transplantation: Outcomes of 35 patients over 27 years in one pediatric quaternary hospital.

Liver transplantation (LT) has been used for many years as a therapeutic option for certain inborn errors of metabolism (IEMs). Here we present one institution's 27 years of experience with LT in IEMs. Our objective is to assess the outcomes of IEM patients who have undergone LT, which we hypothesize to be generally successful for prevention of metabolic decompensation.

Trainee perspectives of COVID-19 impact on medical genetics education.

Purpose: The SARS-CoV-2 pandemic abruptly altered medical education and clinical care. This work evaluates trainee perspectives of the impact of the pandemic on medical genetics education.

Methods: A Qualtrics survey was sent to physician trainees who rotated in genetics before or midpandemic.

Loss-of-function of Endothelin receptor type A results in Oro-Oto-Cardiac syndrome.

Craniofacial morphogenesis is regulated in part by signaling from the Endothelin receptor type A (EDNRA). Pathogenic variants in EDNRA signaling pathway components EDNRA, GNAI3, PCLB4, and EDN1 cause Mandibulofacial Dysostosis with Alopecia (MFDA), Auriculocondylar syndrome (ARCND) 1, 2, and 3, respectively. However, cardiovascular development is normal in MFDA and ARCND individuals, unlike Ednra knockout mice.

Persistent dyslipidemia in treatment of lysosomal acid lipase deficiency.

Background: Lysosomal acid lipase deficiency (LALD) is an autosomal recessive inborn error of lipid metabolism characterized by impaired lysosomal hydrolysis and consequent accumulation of cholesteryl esters and triglycerides. The phenotypic spectrum is diverse, ranging from severe, neonatal onset failure to thrive, hepatomegaly, hepatic fibrosis, malabsorption and adrenal insufficiency to childhood-onset hyperlipidemia, hepatomegaly, and hepatic fibrosis. Sebelipase alfa enzyme replacement has been approved by the Food and Drug Administration for use in LALD after demonstrating dramatic improvement in transaminitis and dyslipidemia with initiation of enzyme replacement therapy.

QUALITY IMPROVEMENT: Supporting a hospital in difficulty: -experience of a '-buddying' agreement to implement a new medical pathway.

Increased NHS regulation has identified many healthcare organisations with operational and/or financial difficulties. Although the causes are often complex, most cases are effectively managed internally with limited input from external agencies. How best to support the few organisations needing additional support has not been established.

Patterning Three-Dimensional Hydrogel Microenvironments Using Hyperbranched Polyglycerols for Independent Control of Mesh Size and Stiffness.

The extracellular matrix is an environment rich with structural, mechanical, and molecular signals that can impact cell biology. Traditional approaches in hydrogel biomaterial design often rely on modifying the concentration of cross-linking groups to adjust mechanical properties. However, this strategy provides limited capacity to control additional important parameters in 3D cell culture such as microstructure and molecular diffusivity.