Family Lore, a Variant of Uncertain Significance, and CADASIL.

An infant presents in extremis. After the medical team stabilizes him, the race is on to figure out why he got so sick in the first place. The consulting genetics team thinks that it is unlikely his problems are due to a genetic cause, but his extreme, confounding presentation is enough to justify trio exome sequencing.

Telegenetics to provide comprehensive prenatal diagnosis.

Telehealth is an effective way to increase access to genetic services and can address several challenges, including geographic barriers, a shortage of interpreter services, and workforce issues, especially for prenatal diagnosis. The addition of prenatal telegenetics to current workflows shows promise in enhancing the delivery of genetic counseling and testing in prenatal care, providing accessibility, accuracy, patient satisfaction, and cost-effectiveness. Further research is needed to explore long-term patient outcomes and the evolving role of telehealth for prenatal diagnosis.

A rare description of pure partial trisomy of 16q12.2q24.3 and review of the literature.

Trisomy 16 is the most common autosomal trisomy in humans, which is almost uniformly embryonic lethal. Partial trisomy 16 including a segment of the long arm of chromosome 16 is occasionally compatible with life and has been associated with severe congenital defects, growth retardation, and early lethality. Segmental trisomy of 16q is usually described concomitantly with partial monosomy of another chromosome, often resulting from a parental balanced translocation.

The sixth international RASopathies symposium: Precision medicine-From promise to practice.

The RASopathies are a group of genetic disorders that result from germline pathogenic variants affecting RAS-mitogen activated protein kinase (MAPK) pathway genes. RASopathies share RAS/MAPK pathway dysregulation and share phenotypic manifestations affecting numerous organ systems, causing lifelong and at times life-limiting medical complications. RASopathies may benefit from precision medicine approaches.

Homozygous/compound heterozygote RYR1 gene variants: Expanding the clinical spectrum.

The ryanodine receptor 1 (RYR1) is a calcium release channel essential for excitation-contraction coupling in the sarcoplasmic reticulum of skeletal muscles. Dominant variants in the RYR1 have been well associated with the known pharmacogenetic ryanodinopathy and malignant hyperthermia. With the era of next-generation gene sequencing and growing number of causative variants, the spectrum of ryanodinopathies has been evolving with dominant and recessive variants presenting with RYR1-related congenital myopathies such as central core disease, minicore myopathy with external ophthalmoplegia, core-rod myopathy, and congenital neuromuscular disease.

Phenotypic expansion in - a common cause of intellectual disability in females.

De variants in account for 1-3% of unexplained intellectual disability (ID) cases and are amongst the most common causes of ID especially in females. Forty-seven patients (44 females, 3 males) have been described. We identified 31 additional individuals carrying 29 unique variants, including 30 postnatal individuals with complex clinical presentations of developmental delay or ID, and one fetus with abnormal ultrasound findings.

Attitudes Toward and Uptake of Prenatal Genetic Screening and Testing in Twin Pregnancies.

The rate of twinning is rising and since the introduction of non-invasive prenatal testing, interest in and uptake of genetic screening and testing in twin pregnancies has not been investigated. This study aimed to explore the attitudes toward and uptake of current prenatal genetic screening and diagnostic testing options for fetal aneuploidy in twin pregnancies. Women being seen for genetic counseling with twin gestations were recruited for participation in a descriptive study with questionnaire (n = 42) and semi-structured phone interview (n = 15).

Genesurance Counseling: Patient Perspectives.

Genetic counselors (GCs) have reported an increase in discussion of insurance-related, or "genesurance," topics during genetic counseling sessions. Despite increasing frequency, there have been no studies examining patient expectations of GCs in these discussions. This study aimed to explore patient expectations of GCs in these discussions, as well as examine factors that may impact expectations.

Offering Prenatal Screening in the Age of Genomic Medicine: A Practical Guide.

Aims: In September, 2015, Mayo Clinic convened a panel of national thought leaders on prenatal screening, medical genetics, and obstetrics and gynecology practice.

Results: During the 2-day symposium, participants discussed the implications of the shift toward broader prenatal screening using cell-free placental DNA in maternal serum (cfDNA screening). Key topics included challenges around the pace of change in the prenatal screening market, uncertainty around reimbursement, meeting the need for patient counseling, and potential challenges in interpreting and returning cfDNA screening results.

Congenital heart defects and left ventricular non-compaction in males with loss-of-function variants in NONO.

Background: The non-POU domain containing octamer-binding gene (NONO) is located on chromosome Xq13.1 and encodes a member of a small family of RNA-binding and DNA-binding proteins that perform a variety of tasks involved in RNA synthesis, transcriptional regulation and DNA repair. Loss-of-function variants in NONO have been described as a cause of intellectual disability in males but have not been described in association with congenital heart defects or cardiomyopathy.

Genetic counseling for men with recurrent pregnancy loss or recurrent implantation failure due to abnormal sperm chromosomal aneuploidy.

Purpose: The purpose of this study is to review recurrent pregnancy loss (RPL) due to sperm chromosomal abnormalities and discuss the genetic counseling that is required for men with sperm chromosomal abnormalities.

Method: The literature was reviewed, and a genetic counselor lends her expertise as to how couples with RPL and sperm chromosomal abnormalities ought to be counseled. The review of the literature was performed using MEDLINE.

Obstetrician and Gynecologist Utilization of the Noninvasive Prenatal Testing Expanded Option.

Objective Noninvasive prenatal testing (NIPT) enables the detection of common fetal aneuploidies such as trisomy 21, trisomy 18, trisomy 13, and sex chromosome abnormalities via analysis of cell-free fetal DNA circulating in maternal serum. In October 2013, the option to screen for additional trisomies and select microdeletion syndromes became clinically available. The complex testing methods, oftentimes unclear clinical utility of results, and lack of professional guidelines renders it challenging for clinicians to keep abreast of evolving prenatal screening options.

DNA sequence analysis and genotype-phenotype assessment in 71 patients with syndromic hearing loss or auditory neuropathy.

Objectives: Aetiological assessment of 71 probands whose clinical presentation suggested a genetic syndrome or auditory neuropathy.

Methods: Sanger sequencing was performed on DNA isolated from peripheral blood or lymphoblastoid cell lines. Genes were selected for sequencing based on each patient's clinical presentation and suspected diagnosis.

Counseling Challenges with Variants of Uncertain Significance and Incidental Findings in Prenatal Genetic Screening and Diagnosis.

Prenatal genetic screening and testing provides prospective parents information about the health of their fetus. It is offered to find or address an increased risk for chromosomal abnormalities or other genetic conditions in the fetus or to identify the cause of fetal structural abnormalities detected by prenatal imaging. Genome-wide tests, such as the already widely-used chromosomal microarray analysis and emerging diagnostic whole exome and whole genome sequencing, have improved the ability to detect clinically significant findings, but have also increased the chance of detecting incidental findings and variants of uncertain significance.

Basic medical genetics for the otolaryngologist.

Medical genetics is becoming an increasingly important part of the practice of medicine across every medical specialty. For otolaryngologists, understanding the genetic basis of hearing loss, tumors of the head and neck and other otolaryngologic conditions is crucial to effectively incorporating medical genetics information, tools and services into patient care. A clinician who understands the genetic basis of disease, mechanisms of genetic mutation and patterns of inheritance will be positioned to diagnose genetic conditions, interpret genetic test results, assess genetic risks for relatives of patients and refer patients and families for medical genetics and other specialty care.

Knowledge, attitudes, and clinical experience of physicians regarding preimplantation genetic diagnosis for hereditary cancer predisposition syndromes.

Approximately 5-10% of cancers are caused by an inherited predisposition. Individuals affected by hereditary cancer are often concerned about transmitting a predisposition to cancer to their children. Preimplantation genetic diagnosis (PGD) is a technology that allows embryos without a deleterious mutation associated with a hereditary cancer syndrome to be identified and implanted.

Clinical use of array comparative genomic hybridization (aCGH) for prenatal diagnosis in 300 cases.

Objective: To evaluate the use of array comparative genomic hybridization (aCGH) for prenatal diagnosis, including assessment of variants of uncertain significance, and the ability to detect abnormalities not detected by karyotype, and vice versa.

Methods: Women undergoing amniocentesis or chorionic villus sampling (CVS) for karyotype were offered aCGH analysis using a targeted microarray. Parental samples were obtained concurrently to exclude maternal cell contamination and determine if copy number variants (CNVs) were de novo, or inherited prior to issuing a report.

Pre- and postnatal genetic testing by array-comparative genomic hybridization: genetic counseling perspectives.

Recently, a new genetic test has been developed that allows a more detailed examination of the genome when compared with a standard chromosome analysis. Array comparative genomic hybridization (CGH microarray; also known as chromosome microarray analysis) in effect, combines chromosome and fluorescence in situ hybridization analyses allowing detection not only of aneuploidies, but also of all known microdeletion and microduplication disorders, including telomere rearrangements. Since 2004, this testing has been available in the Medical Genetics Laboratory at Baylor College of Medicine for postnatal evaluation and diagnosis of individuals with suspected genomic disorders.

Prenatal diagnosis of chromosomal abnormalities using array-based comparative genomic hybridization.

Purpose: This study was designed to evaluate the feasibility of using a targeted array-CGH strategy for prenatal diagnosis of genomic imbalances in a clinical setting of current pregnancies.

Methods: Women undergoing prenatal diagnosis were counseled and offered array-CGH (BCM V4.0) in addition to routine chromosome analysis.

DNA sequence analysis of GJB2, encoding connexin 26: observations from a population of hearing impaired cases and variable carrier rates, complex genotypes, and ethnic stratification of alleles among controls.

Mutations in GJB2 are associated with hereditary hearing loss. DNA sequencing of GJB2 in a cohort of hearing impaired patients and a multi-ethnic control group is reported. Among 610 hearing impaired cases, 43 DNA sequence variations were identified in the coding region of GJB2 including 24 mutations, 8 polymorphisms, 3 unclassified variants (G4D, R127C, M163V), 1 controversial variant (V37I), and 7 novel variants (G12C, N14D, V63A, T86M, L132V, D159, 592_600delinsCAGTGTTCATGACATTC).

Hereditary multiple exostosis and pain.

This study was undertaken to characterize pain in individuals with hereditary multiple exostosis (HME). Two hundred ninety-three patients with HME completed a questionnaire designed to assess pain as well as its impact on their life. Eighty-four percent of participants reported having pain, indicating that pain is a real problem in HME.