Improving Automated Deep Phenotyping Through Large Language Models Using Retrieval Augmented Generation.

Background: Diagnosing rare genetic disorders relies on precise phenotypic and genotypic analysis, with the Human Phenotype Ontology (HPO) providing a standardized language for capturing clinical phenotypes. Traditional HPO tools, such as Doc2HPO and ClinPhen, employ concept recognition to automate phenotype extraction but struggle with incomplete phenotype assignment, often requiring intensive manual review. While large language models (LLMs) hold promise for more context-driven phenotype extraction, they are prone to errors and "hallucinations," making them less reliable without further refinement.

Expanded carrier screening for reproductive risk assessment: An evidence-based practice guideline from the National Society of Genetic Counselors.

Expanded carrier screening (ECS) intends to broadly screen healthy individuals to determine their reproductive chance for autosomal recessive (AR) and X-linked (XL) conditions with infantile or early-childhood onset, which may impact reproductive management (Committee Opinion 690, Obstetrics and Gynecology, 2017, 129, e35). Compared to ethnicity-based screening, which requires accurate knowledge of ancestry for optimal test selection and appropriate risk assessment, ECS panels consist of tens to hundreds of AR and XL conditions that may be individually rare in various ancestries but offer a comprehensive approach to inherited disease screening. As such, the term "equitable carrier screening" may be preferable.

Implication of chromosomal microarray analysis prior to in-utero repair of fetal open neural tube defect.

Objective: In-utero repair of open neural tube defects (ONTD) is an accepted treatment option with demonstrated superior outcome for eligible patients. While current guidelines recommend genetic testing by chromosomal microarray analysis (CMA) when a major congenital anomaly is detected prenatally, the requirement for an in-utero repair, based on the Management of Myelomeningocele Study (MOMS) criteria, is a normal karyotype. In this study, we aimed to evaluate if CMA should be recommended as a prerequisite for in-utero ONTD repair.

Information is power: The experiences, attitudes and needs of individuals who chose to have prenatal genomic sequencing for fetal anomalies.

Objective: This study sought to evaluate the experiences of individuals who chose to participate in a study and receive prenatal genomic sequencing (pGS) for fetuses with congenital structural anomalies.

Method: Individuals who received research results of prenatal sequencing were invited to participate in semi-structured interviews about their experiences. A constructivist grounded theory approach was used to code and analyze interviews.

Clinical characterization of individuals with the distal 1q21.1 microdeletion.

Distal 1q21.1 microdeletions have shown highly variable clinical expressivity and incomplete penetrance, with affected individuals manifesting a broad spectrum of nonspecific features. The goals of this study were to better describe the phenotypic spectrum of patients with distal 1q21.

Prenatal testing in pregnancies conceived by in vitro fertilization with pre-implantation genetic testing.

Objective: Women with pregnancies resulting from in vitro fertilization (IVF) with normal pre-implantation genetic testing for aneuploidy (PGT-A) are advised to undergo prenatal screening and testing during pregnancy. It is not well known how many follow these recommendations. Our objective was to study prenatal testing decisions made by women with pregnancies conceived through IVF with PGT-A.

Bi-allelic Mutations in NADSYN1 Cause Multiple Organ Defects and Expand the Genotypic Spectrum of Congenital NAD Deficiency Disorders.

Birth defects occur in up to 3% of all live births and are the leading cause of infant death. Here we present five individuals from four unrelated families, individuals who share similar phenotypes with disease-causal bi-allelic variants in NADSYN1, encoding NAD synthetase 1, the final enzyme of the nicotinamide adenine dinucleotide (NAD) de novo synthesis pathway. Defects range from the isolated absence of both kidneys to multiple malformations of the vertebrae, heart, limbs, and kidney, and no affected individual survived for more than three months postnatally.

A family affair-Severe fetal and neonatal hemolytic anemia due to novel alpha-spectrin mutations in two siblings.

Hereditary spherocytosis (HS) is the most common cause of inherited, nonimmune hemolytic anemia. When inherited in an autosomal dominant fashion, the anemia is typically mild. However, severe, transfusion-dependent anemia is seen in autosomal recessive HS, which is often associated with deficient or absent red blood cell membrane protein alpha-spectrin.

Clinical exome sequencing for fetuses with ultrasound abnormalities and a suspected Mendelian disorder.

Background: Exome sequencing is now being incorporated into clinical care for pediatric and adult populations, but its integration into prenatal diagnosis has been more limited. One reason for this is the paucity of information about the clinical utility of exome sequencing in the prenatal setting.

Methods: We retrospectively reviewed indications, results, time to results (turnaround time, TAT), and impact of exome results for 146 consecutive "fetal exomes" performed in a clinical diagnostic laboratory between March 2012 and November 2017.

Reproductive genetic counseling challenges associated with diagnostic exome sequencing in a large academic private reproductive genetic counseling practice.

Objective: Diagnostic whole exome sequencing (WES) is rapidly entering clinical genetics, but experience with reproductive genetic counseling aspects is limited. The purpose of this study was to retrospectively review and report on our experience with preconception and prenatal genetic counseling for diagnostic WES.

Method: We performed a retrospective chart review over 34 months in a large private prenatal genetic counseling practice and analyzed data for referral indications, findings, and results of genetic counseling related to diagnostic WES.

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.

Giant avascular hepatocellular carcinoma mimicking metastatic tumor.

We have described the radiographic features of a case of solitary giant hepatocellular carcinoma in a noncirrhotic liver. It was angiographically avascular and resembled a massive metastatic tumor. Most hepatocellular carcinomas appear highly vascular on angiography.

Serum levels of a filaricide, diethylcarbamazine citrate, in cats following different routes of administration.

We have reported the blood levels of diethycarbamazine (DEC) and the persistence of the drug in the circulation for several routes and protocols of DEC administration in cats. This information will be helpful in studies using the Brugia-cat model for studies of experimental chemotherapy.

Effects of selected cholinergic and anticholinergic drugs on Brugia malayi (Nematoda).

1. Several drugs were tested as inhibitors of the body movements of adult Brugia malayi. 2.