Background Disease severity is important when considering genes for inclusion on reproductive expanded carrier screening (ECS) panels. We applied a validated and previously published algorithm that classifies diseases into four severity categories (mild, moderate, severe, and profound) to 176 genes screened by ECS. Disease traits defining severity categories in the algorithm were then mapped to four severity‐related ECS panel design criteria cited by the American College of Obstetricians and Gynecologists (ACOG). Methods Eight genetic counselors (GCs) and four medical geneticists (MDs) applied the severity algorithm to subsets of 176 genes. MDs and GCs then determined by group consensus how each of these disease traits mapped to ACOG severity criteria, enabling determination of the number of ACOG severity criteria met by each gene. Results Upon consensus GC and MD application of the severity algorithm, 68 (39%) genes were classified as profound, 71 (40%) as severe, 36 (20%) as moderate, and one (1%) as mild. After mapping of disease traits to ACOG severity criteria, 170 out of 176 genes (96.6%) were found to meet at least one of the four criteria, 129 genes (73.3%) met at least two, 73 genes (41.5%) met at least three, and 17 genes (9.7%) met all four. Conclusion This study classified the severity of a large set of Mendelian genes by collaborative clinical expert application of a trait‐based algorithm. Further, it operationalized difficult to interpret ACOG severity criteria via mapping of disease traits, thereby promoting consistency of ACOG criteria interpretation.

Purpose of reviewWith the advent of precision medicine and demand for genomic testing information, we may question whether it is time to offer genetic testing to our patients with Parkinson disease (PD). This review updates the current genetic landscape of PD, describes what genetic testing may offer, provides strategies for evaluating whom to test, and provides resources for the busy clinician.Recent findingsPatients with PD and their relatives, in various settings, have expressed an interest in learning their PD genetic status; however, physicians may be hesitant to widely offer testing due to the perceived low clinical utility of PD genetic test results. The rise of clinical trials available for patients with gene-specific PD and emerging information on genotype-phenotype correlations are starting to shift this discussion about testing.SummaryBy learning more about the various genetic testing options for PD and utility of results for patients and their care, clinicians may become more comfortable with widespread PD genetic testing in the research and clinical setting.

Approximately 5% to 10% of individuals with Parkinson's disease (PD) carry an identifiable pathogenic variant (Kim & Alcalay, 2017). Individuals with PD, a family history of PD, or who are of certain ethnic backgrounds, such as Ashkenazi Jewish ancestry, are more likely than the general population to carry a pathogenic variant in the LRRK2 (OMIM 609007) or GBA (OMIM 606463) genes (Cook

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Introduction:There have been no specific guidelines regarding which genes should be tested in the clinical setting for Parkinson's disease (PD) or parkinsonism. We evaluated the types of clinical genetic testing offered for PD as the first step of our gene curation. Methods: The National Institutes of Health (NIH) Genetic Testing Registry (GTR) was queried on 12/7/2020 to identify current commercial PD genetic test offerings by clinical laboratories, internationally. Results: We identified 502 unique clinical genetic tests for PD, from 28 Clinical Laboratory Improvement Amendments (CLIA)-approved clinical laboratories. These included 11 diagnostic PD panels. The panels were notable for their differences in size, ranging from 5 to 62 genes. Five genes for variant query were included in all panels (SNCA, PRKN, PINK-1, PARK7 (DJ1), and LRRK2). Notably, the addition of the VPS35 and GBA genes was variable. Panel size differences stemmed from inclusion of genes linked to atypical parkinsonism and dystonia disorders, and genes in which the link to PD causation is controversial. Conclusion: There is an urgent need for expert opinion regarding which genes should be included in a commercial laboratory multi-gene panel for PD.

There are multiple autosomal recessive disorders in which carriers may be at risk for other diseases. This observation calls into question the previous understanding that carriers of autosomal recessive disorders escape clinical consequences. We also know that childhood genetic conditions may have adult disease counterparts (Zimran et al., The Israel Medical Association Journal: IMAJ, 16(11), 723-724, 2014). Individuals who have Gaucher disease and carriers of the disorder are at increased risk for a seemingly unrelated and complex neurological condition, Parkinson disease. Parkinson disease is, in part, caused by the same mutations in the GBA gene that lead to Gaucher disease, and the two conditions are thought to have shared pathophysiology. Briefly reviewed are how these two diseases historically became linked, where their paths cross, potential problems and considerations in disclosure of the link, and current guidelines and research in this area. Genetic counseling experience with a large Parkinson disease cohort is used as a starting point to question the state of clinical and nonclinical practice in disclosing this unusual connection We conclude that more research and discussion are needed to inform practice regarding the crossroads of Gaucher and Parkinson disease.

We have greater knowledge about the genetic contributions to Parkinson’s disease (PD) with major gene discoveries occurring in the last few decades and the identification of risk alleles revealed by genome-wide association studies (GWAS). This has led to increased genetic testing fueled by both patient and consumer interest and emerging clinical trials targeting genetic forms of the disease. Attention has turned to prodromal forms of neurodegenerative diseases, including PD, resulting in assessments of individuals at risk, with genetic testing often included in the evaluation. These trends suggest that neurologists, clinical geneticists, genetic counselors, and other clinicians across primary care and various specialties should be prepared to answer questions about PD genetic risks and test results. The aim of this article is to provide genetic information for professionals to use in their communication to patients and families who have experienced PD. This includes up-to-date information on PD genes, variants, inheritance patterns, and chances of disease to be used for risk counseling, as well as insurance considerations and ethical issues.

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