Expanded carrier screening for inherited genetic disease using exome and genome sequencing.

The goal of this study was to assess the feasibility of using exome (ES) and genome sequencing (GS) in guiding preconception genetic screening (PCGS) for couples who are planning to conceive by creating a workflow for identifying risk alleles for autosomal recessive (AR) and X-linked (XL) disorders without the constraints of a predetermined, targeted gene panel. There were several limitations and challenges related to reporting and the technical aspects of ES and GS, which are listed in the discussion. We selected 150 couples from a cohort of families (trios) enrolled in a research protocol where the goal was to define the genetic etiology of disease in an affected child.

FGF12 copy number variant associated with epileptic encephalopathy.

FGF12 related epilepsy presents with variable phenotypes. We report another patient with a duplication involving the FGF12 gene who presented similar to other published cases having normal early development and responded to phenytoin.

Underreporting alteration by clinical sequencing: Integrative patho-genomic analysis captured /INI-1 deficiency in a vulvar yolk sac tumor.

•/INI1-deficient gynecologic tumors are rare and clinically aggressive. A subset shows primitive yolk sac tumor features.•Due to technical limitation of next generation sequencing (NGS) and interlaboratory variability in sequencing methodologies and analytical pipelines, deficiency caused by somatic copy number variations (SCNV) may be underreported by NGS.

Implementation, Evolution, and Laboratory Performance of Methods-Based Proficiency Testing for Next-Generation Sequencing Detection of Germline Sequence Variants.

Context.—: Next-generation sequencing (NGS)-based assays are used for diagnosis of diverse inherited disorders. Limited data are available pertaining to interlaboratory analytical performance of these assays.

Preparing for the unexpected: Recommendations for returning secondary findings in late-stage cancer care.

Purpose: We conducted qualitative interviews with patients with cancer and providers to identify gaps in clinical care and highlight care delivery solutions for the return of secondary germline findings.

Methods: Twelve patients and 19 cancer providers from the United States were interviewed between January 2019 and May 2021. Interviews elicited feedback about patient information needs, emotional responses to secondary findings, and recommendations for improving pre-test education.