Analysis of financial barriers experienced by prospective genetic counseling students.

Purpose: High costs of applying to genetic counseling graduate programs (GCGPs) are likely a barrier to workforce diversification. We sought to determine application costs and assess differences between individuals of historically underrepresented racial and ethnic backgrounds in medicine (hURM) and non-hURM applicants.

Methods: Applicants to GCGPs between 2005 to 2020 were surveyed about application history, related expenses, volunteer hours, and financial resources; 383 responses were analyzed.

Clinical implications of conflicting variant interpretations in the cancer genetics clinic.

Purpose: The aim of this study was to describe the clinical impact of commercial laboratories issuing conflicting classifications of genetic variants.

Methods: Results from 2000 patients undergoing a multigene hereditary cancer panel by a single laboratory were analyzed. Clinically significant discrepancies between the laboratory-provided test reports and other major commercial laboratories were identified, including differences between pathogenic/likely pathogenic and variant of uncertain significance (VUS) classifications, via review of ClinVar archives.

Non-mosaic trisomy 22 and congenital heart surgery using the shared decision making model: a case report.

Background: Liveborn infants with non-mosaic trisomy 22 are rarely described in the medical literature. Reported lifespan of these patients ranges from minutes to 3 years, with the absence of cardiac anomalies associated with longer-term survival. The landscape for offering cardiac surgery to patients with rare autosomal trisomies is currently evolving, as has been demonstrated recently in trisomies 13 and 18.

When moments matter: Finding answers with rapid exome sequencing.

Background: When time is of the essence in critical care cases, a fast molecular diagnosis is often necessary to help health care providers quickly determine best next steps for treatments, prognosis, and counseling of their patients. In this paper, we present the diagnostic rates and improved quality of life for patients undergoing clinical rapid exome sequencing.

Methods: The clinical histories and results of 41 patients undergoing rapid exome sequencing were retrospectively reviewed.

Diagnostic utility of transcriptome sequencing for rare Mendelian diseases.

Purpose: We investigated the value of transcriptome sequencing (RNAseq) in ascertaining the consequence of DNA variants on RNA transcripts to improve the diagnostic rate from exome or genome sequencing for undiagnosed Mendelian diseases spanning a wide spectrum of clinical indications.

Methods: From 234 subjects referred to the Undiagnosed Diseases Network, University of California-Los Angeles clinical site between July 2014 and August 2018, 113 were enrolled for high likelihood of having rare undiagnosed, suspected genetic conditions despite thorough prior clinical evaluation. Exome or genome sequencing and RNAseq were performed, and RNAseq data was integrated with genome sequencing data for DNA variant interpretation genome-wide.

ALG11-CDG syndrome: Expanding the phenotype.

ALG11-Congenital Disorder of Glycosylation (ALG11-CDG, also known as congenital disorder of glycosylation type Ip) is an inherited inborn error of metabolism due to abnormal protein and lipid glycosylation. We describe two unrelated patients with ALG11-CDG due to novel mutations, review the literature of previously described affected individuals, and further expand the clinical phenotype. Both affected individuals reported here had severe psychomotor disabilities and epilepsy.

Orbital infections: a complete cycle 7-year audit and a management guideline.

Objectives: Orbital infections are regularly encountered and are managed by various healthcare disciplines. Sepsis of the orbit and adjacent tissues can be associated with considerable acute complication and long-term sequelae. Therefore, prompt recognition and management of this condition are crucial.

De novo loss-of-function variants in STAG2 are associated with developmental delay, microcephaly, and congenital anomalies.

The cohesin complex is an evolutionarily conserved multi-subunit protein complex which regulates sister chromatid cohesion during mitosis and meiosis. Additionally, the cohesin complex regulates DNA replication, DNA repair, and transcription. The core of the complex consists of four subunits: SMC1A, SMC3, RAD21, and STAG1/2.

Two cases of Legg-Perthes and intellectual disability in Tricho-Rhino-Phalangeal syndrome type 1 associated with novel TRPS1 mutations.

Tricho-Rhino-Phalangeal syndrome is a rare autosomal dominant genetic disorder caused by mutations in the TRPS1 gene. This malformation syndrome is characterized by distinctive craniofacial features including sparse scalp hair, bulbous tip of the nose, long flat philtrum, thin upper vermilion border, and protruding ears. Skeletal abnormalities include cone-shaped epiphyses at the phalanges, hip malformations, and short stature.

Colorectal Cancer Incidence Among Young Adults in California.

Colorectal cancer (CRC) incidence has decreased over the past three decades, due largely to screening efforts. Relatively little is known about CRC incidence among the young adult (YA) population ages 20-39, as screening typically commences at age 50 for average-risk individuals. We examined CRC incidence with a focus on YAs in order to identify high-risk subgroups.

Amelioration of the typical cognitive phenotype in a patient with the 5pter deletion associated with Cri-du-chat syndrome in addition to a partial duplication of CTNND2.

Cri-du-chat is a rare congenital syndrome characterized by intellectual disability, severe speech/developmental delay, dysmorphic features, and additional syndromic findings. The etiology of this disorder is well known, and is attributed to a large deletion on chromosome 5 that typically ranges from band 5p15.2 to the short arm terminus.

Diagnosis of cystic fibrosis in the kindred of an infant with CFTR-related metabolic syndrome: importance of follow-up that includes monitoring sweat chloride concentrations over time.

Newly implemented newborn screening (NBS) programs in California have resulted in a large subset of patients in whom at least two cystic fibrosis transmembrane conductance regulator (CFTR) mutations are identified, but subsequent sweat chloride analysis reveals normal or indeterminate values. These patients are diagnosed with CFTR-Related Metabolic Syndrome (CRMS). However, the natural progression and management of these patients are not clearly understood and frequently after the age of 1-year these patients are lost to follow-up with Cystic Fibrosis (CF) Centers.

Clinical and radiological features in young individuals with nevoid basal cell carcinoma syndrome.

Purpose: Nevoid basal cell carcinoma syndrome is an autosomal dominant disorder characterized by multiple basal cell carcinomas, jaw cysts, palmar/plantar pits, spine and rib anomalies, and falx cerebri calcification. Current diagnostic criteria are suboptimal when applied to pediatric populations, as most common symptoms often do not begin to appear until teenage years.

Methods: We studied minor and major clinical features in 30 children/teenagers and compared the findings with 75 adults from 26 families with nevoid basal cell carcinoma syndrome.

An additional patient with mycophenolate mofetil embryopathy: cardiac and facial analyses.

We describe an infant male of Cambodian background who has typical craniofacial features of mycophenolate mofetil (MMF) embryopathy and a complex congenital heart defect (CHD) (double outlet right ventricle, mitral atresia, pulmonic stenosis, and total anomalous pulmonary venous return). Together with four case reports and the 20 patients included in two recent reviews, we report 24 (19 affected, five normal) patients with this pattern of anomalies. Eight (33%) have a CHD, most commonly, conotruncal or aortic arch defects (6/8, 75%).

A p53-independent role of Mdm2 in estrogen-mediated activation of breast cancer cell proliferation.

Introduction: Estrogen receptor positive breast cancers often have high levels of Mdm2. We investigated if estrogen signaling in such breast cancers occurred through an Mdm2 mediated pathway with subsequent inactivation of p53.

Methods: We examined the effect of long-term 17β-estradiol (E2) treatment (five days) on the p53-Mdm2 pathway in estrogen receptor alpha (ERα) positive breast cancer cell lines that contain wild-type p53 (MCF-7 and ZR75-1).