Kemppainen, Jennifer

Abstract Genetic counseling assistants (GCAs) support genetic counselors (GCs) and genetics clinic workflows, but their potential roles in pretest genetic counseling for rare diseases have not been explored. A pilot within the Mayo Clinic Center for Individualized Medicine's Genetic Testing and Counseling Clinic (GTAC), which offers predefined tests for patients with rare disease, explored the impact of GCA pretest education on appointment time and patient questions. After training, GCAs met GTAC patients prior to the GC to provide scripted information on genetics concepts, the visit purpose, and the test including result types and disclosure plans. Data from the pilot and a control group were collected and analyzed using descriptive statistics and two‐sided t ‐tests. Patient cohort characteristics did not differ between the two models. When a GCA provided pretest education, the GC spent an average of 11.2 minutes less with the patient during their session compared to visits completed solely by the GC ( p < 0.0001). Total appointment time was not impacted by GCA education. Questions asked to GCAs were often not within GCA scope to answer (72.7%), and some patients asked repetitive questions to both the GC and GCA (63.2%). Reduction in GC time per patient could lead to increased accessibility by allowing additional patients to be seen in a day. Similar models may support GCA professional development while allowing GCs to remove repetitive education from their genetic counseling sessions, leading to less burnout and/or increased job satisfaction. Impact on administrative workflows, access, revenue, patient satisfaction and outcomes and GC/GCA satisfaction and benefits can continue to be explored when trialing models incorporating GCAs in pretest education roles.

Background. Recent studies identified underlying genetic causes in a proportion of patients with various forms of kidney disease. In particular, genetic testing reclassified some focal segmental glomerulosclerosis (FSGS) cases into collagen type 4 (COL4)-related nephropathy. This knowledge has major implications for counseling prospective transplant recipients about recurrence risk and screening biologically related donors. We describe our experience incorporating genetic testing in our kidney transplant multidisciplinary practice. Methods. Patients’ DNA was analyzed using whole exome sequencing for a comprehensive kidney gene panel encompassing 344 genes associated with kidney diseases and candidate genes highly expressed in the kidney. Results were correlated with phenotype by a multidisciplinary committee of nephrologists, renal pathologists, geneticists, and genetic counselors. Between October 2018 and July 2020, 30 recipient and 5 donor candidates completed testing. Results. Among recipient candidates, 24 (80%) carried the diagnosis of FSGS, 2 (6.7%) tubulointerstitial nephritis, and 1 (3.3%) nephrolithiasis, and 3 (10%) had an unknown cause of kidney disease. The yield for pathogenic/likely pathogenic variants was 43.3%, with majority being COL4 variants (53.8%). Among those with FSGS diagnosis, the yield was 10 of 24 (41.6%), with 29% reclassified into a COL4-related nephropathy. Family history of kidney disease was the only clinical characteristic difference between recipients with positive and negative results (76.9 versus 29.4%; P = 0.025). One of 5 donors tested positive for a pathogenic/likely pathogenic variant and was excluded from donation. Conclusions. We conclude that thoughtful use of genetic testing can be valuable for kidney donor selection and transplant recipient management.

Variants in PURA have recently been associated with an autosomal dominant form of PURA-related neurodevelopmental disorders. Using whole exome sequencing, patients with neurological phenotypes including hypotonia, developmental delay, learning disabilities, and seizures were identified to have de novo variants in PURA. We describe a proband with features similar to the previously described cases with PURA variants, but including additional features, such as short stature, delayed bone age, and delayed puberty. Exome sequencing revealed a novel pathogenic nonsense variant, c.190A>T (p.Lys64*; NM_005859), in PURA that was not inherited from the proband’s mother. In the recent literature, a significant number of patients with variants in PURA have been described, but to our knowledge, none of these patients have the delayed bone age and growth plateau observed in the proband. It is therefore possible that the above PURA variant may be responsible for the novel features and thus expands the PURA-related phenotype spectrum.

AbstractWhole exome sequencing (WES) has become a fundamental component of genetic evaluation and diagnosing rare genetic diseases. This test is now offered to patients from a wide variety of cultural backgrounds and in various clinical and research settings. This commentary is a reflection of one group of clinical genetic counselors’ experiences in facilitating WES for patients who come from outside the United States for genetic evaluation and pursue WES. This patient population in our clinic primarily consists of individuals from the Middle East and presents recurrent logistical and counseling challenges. We aim to describe our international patient population, illuminate the challenges we have faced and illustrate how we have addressed these challenges.