Novel Digital Anomalies, Hippocampal Atrophy, and Mutations Expand the Genotypic and Phenotypic Spectra of CNKSR2 in the Houge Type of X-Linked Syndromic Intellectual Development Disorder (MRXSHG).

The Houge type of X-linked syndromic intellectual developmental disorder (MRXSHG) encompasses a spectrum of neurodevelopmental disorders characterized by intellectual disability (ID), language/speech delay, attention issues, and epilepsy. These conditions arise from hemizygous or heterozygous deletions, along with point mutations, affecting CNKSR2, a gene located at Xp22.12.

Transgender identity genetic research: Attitudes, opinions & beliefs among members of the transgender and gender diverse communities.

There is growing interest in investigating genetic explanations for transgender identity. In the spirit of a Community-Engaged Research Framework, which highlights the importance of involving community members who would be impacted by research throughout the entire research process, it is important for researchers to understand transgender and gender expansive individuals' views and concerns regarding the potential harms and benefits of transgender identity genetic research (TIGR). To evaluate the thoughts, opinions, and beliefs in the transgender and gender diverse communities toward TIGR We conducted an online survey study, asking 409 transgender and gender diverse individuals about their views regarding potential benefits and risks of TIGR.

Exome sequencing reveals neurodevelopmental genes in simplex consanguineous Iranian families with syndromic autism.

Background And Objective: Autosomal recessive genetic disorders pose significant health challenges in regions where consanguineous marriages are prevalent. The utilization of exome sequencing as a frequently employed methodology has enabled a clear delineation of diagnostic efficacy and mode of inheritance within multiplex consanguineous families. However, these aspects remain less elucidated within simplex families.

Identification of rare genetic variants in the PCDH genetic family in a cohort of transgender women.

Objective: To study the identification of rare genetic variants in the PCDH genetic family in a cohort of transgender women (TGW) and their potential role in gender identity.

Design: Exome sequencing and functional ontology analysis.

Setting: Outpatient gender health and reproductive endocrinology clinics.

Heterozygous ZNHIT3 variants within the 17q12 recurrent deletion region are associated with Mayer-Rokitansky-Kuster Hauser (MRKH) syndrome.

The molecular basis of mullerian aplasia, also known as Mayer-Rokitansky-Kuster Hauser (MRKH) or congenital absence of the uterus and vagina, is largely unknown. We applied a multifaceted genetic approach to studying the pathogenesis of MRKH including exome sequencing of trios and duos, genome sequencing of families, qPCR, RT-PCR, and Sanger sequencing to detect intragenic deletions, insertions, splice variants, single nucleotide variants, and rearrangements in 132 persons with MRKH. We identified two heterozygous variants in ZNHIT3 localized to a commonly involved CNV region at chromosome 17q12 in two different families with MRKH.

Identification of two novel autism genes, and , in Qatar simplex families through exome sequencing.

This study investigated the genetic underpinnings of autism spectrum disorder (ASD) in a Middle Eastern cohort in Qatar using exome sequencing. The study identified six candidate autism genes in independent simplex families, including both four known and two novel autosomal dominant and autosomal recessive genes associated with ASD. The variants consisted primarily of and homozygous missense and splice variants.

Endogenous estradiol contributes to vascular endothelial dysfunction in premenopausal women with type 1 diabetes.

Background: Endogenous estrogen is cardio-protective in healthy premenopausal women. Despite this favorable action of estrogen, animal models depict a detrimental effect of estradiol on vascular function in the presence of diabetes. The present study sought to determine the role of endogenous estradiol on endothelial function in women with type 1 diabetes.

Coordination of canonical and noncanonical Hedgehog signalling pathways mediated by WDR11 during primordial germ cell development.

WDR11, a gene associated with Kallmann syndrome, is important in reproductive system development but molecular understanding of its action remains incomplete. We previously reported that Wdr11-deficient embryos exhibit defective ciliogenesis and developmental defects associated with Hedgehog (HH) signalling. Here we demonstrate that WDR11 is required for primordial germ cell (PGC) development, regulating canonical and noncanonical HH signalling in parallel.

Providing baseline data for conservation-Heart rate monitoring in captive scimitar-horned oryx.

Heart rate biologging has been successfully used to study wildlife responses to natural and human-caused stressors (e.g., hunting, landscape of fear).

Rare structural variants, aneuploidies, and mosaicism in individuals with Mullerian aplasia detected by optical genome mapping.

The molecular basis of Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome remains largely unknown. Pathogenic variants in WNT4 and HNF1B have been confirmed in a small percent of individuals. A variety of copy number variants have been reported, but causal gene(s) remain to be identified.

Clinical Validation and Diagnostic Utility of Optical Genome Mapping in Prenatal Diagnostic Testing.

The standard-of-care diagnostic prenatal testing includes a combination of cytogenetic methods, such as karyotyping, fluorescence in situ hybridization (FISH), and chromosomal microarray (CMA), using either direct or cultured amniocytes or chorionic villi sampling. However, each technology has its limitations: karyotyping has a low resolution (>5 Mb), FISH is targeted, and CMA does not detect balanced structural variations (SVs). These limitations necessitate the use of multiple tests, either simultaneously or sequentially, to reach a genetic diagnosis.

Adolescent With Concomitant Transverse and Longitudinal Vaginal Septa.

A vaginal septum is a type of Mullerian anomaly that can be longitudinal or transverse, separating the vagina into two canals. Vaginal septa occur due to lack of fusion and recanalization of Mullerian structures, and often present with voiding dysfunction with potential impact on fertility and sexual function. We describe a rare case of concomitant transverse and longitudinal vaginal septa and discuss its presentation.

Interdisciplinary Collaboration Among Nursing and Computer Science to Refine a Pharmacogenetics Clinical Decision Support Tool Via Mobile Application.

In previous work, a prototype clinical decision support mobile application was created that accepts a patient's genomic profile information and provides information and rationale for the prescription of certain oncology medications. The response to the instrument was overwhelmingly positive by healthcare providers in the oncology field who tested the instrument. This article reports on the interdisciplinary collaboration among nursing and computer science to redesign and reimplement a new version of the instrument with expanded functionality and improved usability.

Effects of Tier 1 Class-Wide Function-Related Intervention Teams (CW-FIT) on On-task Group Behavior in a Preschool Classroom.

Disruptive behaviors such as elopement, calling-out, and aggression are often a major barrier to instruction in preschool classrooms. One widely used class-wide behavior management system is Class-Wide Function-Related Intervention Teams (CW-FIT). To date, we could only locate two studies on CW-FIT used in preschool settings which found a therapeutic change in on-task behavior as well rates of teacher praise, teacher reprimands, student socials skills, and student problem behaviors.

Refinement of a pharmacogenomics app for dosing guidelines for oncology: findings from the usability evaluation.

Background: This study extended a precision medicine clinical decision support mobile application (app) for use with oncology medications. Two gene variants ( and ) associated with pharmacogenomic dosing algorithms in oncology was added to a prototype app. Usability of the app was evaluated.

A rigorous genomic interrogation at 1p13.3 reveals 16 autosomal dominant candidate genes in syndromic neurodevelopmental disorders.

Genome-wide chromosomal microarray is extensively used to detect copy number variations (CNVs), which can diagnose microdeletion and microduplication syndromes. These small unbalanced chromosomal structural rearrangements ranging from 1 kb to 10 Mb comprise up to 15% of human mutations leading to monogenic or contiguous genomic disorders. Albeit rare, CNVs at 1p13.

Biallelic variants in WARS1 cause a highly variable neurodevelopmental syndrome and implicate a critical exon for normal auditory function.

Aminoacyl-tRNA synthetases (ARSs) are essential enzymes for faithful assignment of amino acids to their cognate tRNA. Variants in ARS genes are frequently associated with clinically heterogeneous phenotypes in humans and follow both autosomal dominant or recessive inheritance patterns in many instances. Variants in tryptophanyl-tRNA synthetase 1 (WARS1) cause autosomal dominantly inherited distal hereditary motor neuropathy and Charcot-Marie-Tooth disease.

Optical Genome Mapping and Single Nucleotide Polymorphism Microarray: An Integrated Approach for Investigating Products of Conception.

Conventional cytogenetic analysis of products of conception (POC) is of limited utility because of failed cultures, as well as microbial and maternal cell contamination (MCC). Optical genome mapping (OGM) is an emerging technology that has the potential to replace conventional cytogenetic methods. The use of OGM precludes the requirement for culturing (and related microbial contamination).

Sex Differences in Human Immunodeficiency Virus Persistence and Reservoir Size During Aging.

Background: Sex differences in human immunodeficiency virus (HIV) reservoir dynamics remain underexplored.

Methods: Longitudinal samples from virally suppressed midlife women (n = 59, median age 45 years) and age-matched men (n = 31) were analyzed retrospectively. At each time point, we measured sex hormones (by means of enzyme-linked immunosorbent assay) and cellular HIV DNA and RNA (by means of digital droplet polymerase chain reaction).