Evaluation of nasal mucociliary clearance in patients with psoriasis.

Purpose: Psoriasis is an autoimmune pathology characterized by chronic inflammation with known multiorgan involvement. In the literature, there are few studies investigating the effects of psoriasis on upper respiratory tract mucosa. Our aim in our study was to investigate the possible effect of psoriasis disease severity and duration on nasal mucosa.

variants in the non-coding spliceosomal snRNA gene are a frequent cause of syndromic neurodevelopmental disorders.

Around 60% of individuals with neurodevelopmental disorders (NDD) remain undiagnosed after comprehensive genetic testing, primarily of protein-coding genes. Increasingly, large genome-sequenced cohorts are improving our ability to discover new diagnoses in the non-coding genome. Here, we identify the non-coding RNA as a novel syndromic NDD gene.

Genomic multidisciplinary teams: A model for navigating genetic mainstreaming and precision medicine.

Aim: Recent rapid advances in genomics are revolutionising patient diagnosis and management of genetic conditions. However, this has led to many challenges in service provision, education and upskilling requirements for non-genetics health-care professionals and remuneration for genomic testing. In Australia, Medicare funding with a Paediatric genomic testing item for patients with intellectual disability or syndromic features has attempted to address this latter issue.

What is the power of a genomic multidisciplinary team approach? A systematic review of implementation and sustainability.

Due to the increasing complexity of genomic data interpretation, and need for close collaboration with clinical, laboratory, and research expertise, genomics often requires a multidisciplinary team (MDT) approach. This systematic review aims to establish the evidence for effectiveness of the genomic multidisciplinary team, and the implementation components of this model that can inform precision care. MEDLINE, Embase and PsycINFO databases were searched in 2022 and 2023.

Narrowing the diagnostic gap: Genomes, episignatures, long-read sequencing, and health economic analyses in an exome-negative intellectual disability cohort.

Purpose: Genome sequencing (GS)-specific diagnostic rates in prospective tightly ascertained exome sequencing (ES)-negative intellectual disability (ID) cohorts have not been reported extensively.

Methods: ES, GS, epigenetic signatures, and long-read sequencing diagnoses were assessed in 74 trios with at least moderate ID.

Results: The ES diagnostic yield was 42 of 74 (57%).

Functional and Aesthetic Outcomes of Asymmetric Dorsal Preservation for Correction of I-Shaped Crooked Nose Deformity.

Objective: The study was designed to evaluate the effectiveness of the asymmetric dorsal preservation technique for correcting I-shaped crooked nose deformity (CND).

Methods: Patients with I-shaped CND who underwent asymmetric dorsal preservation in the period from September 2020 to September 2021 were included in this retrospective study. The Rhinomanometry and Standardized Cosmesis and Health Nasal Outcomes Survey (SCHNOS) was used to assess the outcomes.

The health care and societal costs of inherited retinal diseases in Australia: a microsimulation modelling study.

Objectives: To estimate the health care and societal costs of inherited retinal diseases (IRDs) in Australia.

Design, Setting, Participants: Microsimulation modelling study based on primary data - collected in interviews of people with IRDs who had ophthalmic or genetic consultations at the Children's Hospital at Westmead or the Save Sight Institute (both Sydney) during 1 January 2019 - 31 December 2020, and of their carers and spouses - and linked Medicare Benefits Schedule (MBS) and Pharmaceutical Benefits Schedule (PBS) data.

Main Outcome Measures: Annual and lifetime costs for people with IRDs and for their carers and spouses, grouped by payer (Australian government, state governments, individuals, private health insurance) and type (health care costs; societal costs: social support, National Disability Insurance Scheme (NDIS), income and taxation, costs associated with caring for family members with IRDs); estimated annual national cost of IRDs.

Comparison of Dorsal Preservation and Dorsal Reduction Rhinoplasty: Analysis of Nasal Patency and Aesthetic Outcomes by Rhinomanometry, NOSE and SCHNOS Scales.

Background: Dorsal preservation techniques have been preferred and gained popularity in recent years. The current study compares the effects of dorsal preservation and dorsal reduction rhinoplasty on nasal patency and aesthetic outcomes by using Patient-Reported Outcome Measures (PROMs) and rhinomanometry. To our knowledge, this is the first study to compare dorsal preservation and dorsal reduction techniques with rhinomanometry.

Patient-Reported Health-Related Quality of Life in Individuals with Inherited Retinal Diseases.

Purpose: To evaluate the impact of inherited retinal diseases (IRDs) on quality of life (QoL) using multiattributable health utilities derived from primary patient data.

Design: Cross-sectional observational study.

Participants: Seventy adult patients (mean age, 42.

De Novo ZMYND8 variants result in an autosomal dominant neurodevelopmental disorder with cardiac malformations.

Purpose: ZMYND8 encodes a multidomain protein that serves as a central interactive hub for coordinating critical roles in transcription regulation, chromatin remodeling, regulation of super-enhancers, DNA damage response and tumor suppression. We delineate a novel neurocognitive disorder caused by variants in the ZMYND8 gene.

Methods: An international collaboration, exome sequencing, molecular modeling, yeast two-hybrid assays, analysis of available transcriptomic data and a knockdown Drosophila model were used to characterize the ZMYND8 variants.

Whole Genome Sequencing, Focused Assays and Functional Studies Increasing Understanding in Cryptic Inherited Retinal Dystrophies.

The inherited retinal dystrophies (IRDs) are a clinically and genetically complex group of disorders primarily affecting the rod and cone photoreceptors or other retinal neuronal layers, with emerging therapies heralding the need for accurate molecular diagnosis. Targeted capture and panel-based strategies examining the partial or full exome deliver molecular diagnoses in many IRD families tested. However, approximately one in three families remain unsolved and unable to obtain personalised recurrence risk or access to new clinical trials or therapy.

Human iPSC-Derived Retinal Organoids and Retinal Pigment Epithelium for Novel Intronic Variant Assessment for Therapy Suitability.

The RPGR gene encodes Retinitis Pigmentosa GTPase Regulator, a known interactor with ciliary proteins, which is involved in maintaining healthy photoreceptor cells. Variants in RPGR are the main contributor to X-linked rod-cone dystrophy (RCD), and RPGR gene therapy approaches are in clinical trials. Hence, elucidation of the pathogenicity of novel RPGR variants is important for a patient therapy opportunity.

Standardized practices for RNA diagnostics using clinically accessible specimens reclassifies 75% of putative splicing variants.

Purpose: Genetic variants causing aberrant premessenger RNA splicing are increasingly being recognized as causal variants in genetic disorders. In this study, we devise standardized practices for polymerase chain reaction (PCR)-based RNA diagnostics using clinically accessible specimens (blood, fibroblasts, urothelia, biopsy).

Methods: A total of 74 families with diverse monogenic conditions (31% prenatal-congenital onset, 47% early childhood, and 22% teenage-adult onset) were triaged into PCR-based RNA testing, with comparative RNA sequencing for 19 cases.

TUBB3 Arg262His causes a recognizable syndrome including CFEOM3, facial palsy, joint contractures, and early-onset peripheral neuropathy.

Microtubules are formed from heterodimers of alpha- and beta-tubulin, each of which has multiple isoforms encoded by separate genes. Pathogenic missense variants in multiple different tubulin isoforms cause brain malformations. Missense mutations in TUBB3, which encodes the neuron-specific beta-tubulin isotype, can cause congenital fibrosis of the extraocular muscles type 3 (CFEOM3) and/or malformations of cortical development, with distinct genotype-phenotype correlations.

Paediatric genomic testing: Navigating genomic reports for the general paediatrician.

Monogenic rare disorders contribute significantly to paediatric morbidity and mortality, and elucidation of the underlying genetic cause may have benefits for patients, families and clinicians. Advances in genomic technology have enabled diagnostic yields of up to 50% in some paediatric cohorts. This has led to an increase in the uptake of genetic testing across paediatric disciplines.

PPA2-associated sudden cardiac death: extending the clinical and allelic spectrum in 20 new families.

Purpose: Biallelic hypomorphic variants in PPA2, encoding the mitochondrial inorganic pyrophosphatase 2 protein, have been recently identified in individuals presenting with sudden cardiac death, occasionally triggered by alcohol intake or a viral infection. Here we report 20 new families harboring PPA2 variants.

Methods: Synthesis of clinical and molecular data concerning 34 individuals harboring five previously reported PPA2 variants and 12 novel variants, 11 of which were functionally characterized.

Genome sequencing in congenital cataracts improves diagnostic yield.

Congenital cataracts are one of the major causes of childhood-onset blindness around the world. Genetic diagnosis provides benefits through avoidance of unnecessary tests, surveillance of extraocular features, and genetic family information. In this study, we demonstrate the value of genome sequencing in improving diagnostic yield in congenital cataract patients and families.

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.

Hearing screening outcomes in neonates of SARS-CoV-2 positive pregnant women.

Objective: The current study aimed to investigate possible association of maternal SARS-CoV-2 with newborn hearing loss. We compared hearing screening outcomes in neonates born to women with positive SARS-CoV-2 PCR test results during pregnancy with healthy controls.

Methods: Neonates born between April and December 2020 in our hospital to mothers with positive SARS-CoV-2 PCR test results during pregnancy were included in this study.

Maternal hypertension, pre-eclampsia, eclampsia and newborn hearing: A retrospective analysis of 454 newborns.

Objective: Maternal hypertension and preeclampsia have been related to sensorineural hearing loss in newborns. To investigate potential connections, we compared newborn hearing screening (NHS) results from newborns of mothers with chronic hypertension, preeclampsia, and eclampsia with results from newborns of healthy controls. The present study is unique with regard to its large sample size and the analysis of the possible effects of three different hypertensive disorders on newborn hearing.