JARID2 haploinsufficiency is associated with a clinically distinct neurodevelopmental syndrome.

PURPOSE: JARID2, located on chromosome 6p22.3, is a regulator of histone methyltransferase complexes that is expressed in human neurons. So far, 13 individuals sharing clinical features including intellectual disability (ID) were reported with de novo heterozygous deletions in 6p22-p24 encompassing the full length JARID2 gene (OMIM 601594). However, all published individuals to date have a deletion of at least one other adjoining gene, making it difficult to determine if JARID2 is the critical gene responsible for the shared features. We aim to confirm JARID2 as a human disease gene and further elucidate the associated clinical phenotype. METHODS: Chromosome microarray analysis, exome sequencing, and an online matching platform (GeneMatcher) were used to identify individuals with single-nucleotide variants or deletions involving JARID2. RESULTS: We report 16 individuals in 15 families with a deletion or single-nucleotide variant in JARID2. Several of these variants are likely to result in haploinsufficiency due to nonsense-mediated messenger RNA (mRNA) decay. All individuals have developmental delay and/or ID and share some overlapping clinical characteristics such as facial features with those who have larger deletions involving JARID2. CONCLUSION: We report that JARID2 haploinsufficiency leads to a clinically distinct neurodevelopmental syndrome, thus establishing gene-disease validity for the purpose of diagnostic reporting.

Haploinsufficiency of PRR12 causes a spectrum of neurodevelopmental, eye, and multisystem abnormalities.

PURPOSE: Proline Rich 12 (PRR12) is a gene of unknown function with suspected DNA-binding activity, expressed in developing mice and human brains. Predicted loss-of-function variants in this gene are extremely rare, indicating high intolerance of haploinsufficiency. METHODS: Three individuals with intellectual disability and iris anomalies and truncating de novo PRR12 variants were described previously. We add 21 individuals with similar PRR12 variants identified via matchmaking platforms, bringing the total number to 24. RESULTS: We observed 12 frameshift, 6 nonsense, 1 splice-site, and 2 missense variants and one patient with a gross deletion involving PRR12. Three individuals had additional genetic findings, possibly confounding the phenotype. All patients had developmental impairment. Variable structural eye defects were observed in 12/24 individuals (50%) including anophthalmia, microphthalmia, colobomas, optic nerve and iris abnormalities. Additional common features included hypotonia (61%), heart defects (52%), growth failure (54%), and kidney anomalies (35%). PrediXcan analysis showed that phecodes most strongly associated with reduced predicted PRR12 expression were enriched for eye- (7/30) and kidney- (4/30) phenotypes, such as wet macular degeneration and chronic kidney disease. CONCLUSION: These findings support PRR12 haploinsufficiency as a cause for a novel disorder with a wide clinical spectrum marked chiefly by neurodevelopmental and eye abnormalities.

Genetic counseling clinical documentation: Practice Resource of the National Society of Genetic Counselors.

Clinical documentation is an important extension of a genetic counseling encounter. The traditional types of clinical documentation include the clinical visit note (including follow-up visit note), letter to the referring physician, letter to the patient, and result summary to the patient and referring physician. Increasing patient volumes, new genetic counseling service delivery models, transition to electronic medical records (EMR), new specialty clinics in genetics, and advances in genetic testing technologies challenge the practice of writing multiple types of clinical documents. This practice resource (PR) seeks to provide best practices for U.S.-based genetic counselors to write efficient and comprehensive clinical documentation using a hybrid clinical document designed to facilitate communication between individual providers, providers, and patients/families, and providers and payers. The content of the hybrid clinical documentation will vary by genetic specialty but may include a summary of genetic services evaluation, genetic testing options and eligibility information, genetic test results, potential risks for genetic conditions, implications for family members, and medical management recommendations. An outline of a general hybrid document along with examples of hybrid clinic notes for three types of genetic counseling specialties is included in this document.

Impacts of genesurance considerations on genetic counselors' practice and attitudes.

Genesurance counseling has been identified as an integral part of many genetic counseling sessions, but little is known about the workflow impacts and genetic counselor perceptions of genesurance-related tasks. In this study, we aimed to characterize how insurance and billing considerations for genetic testing are being incorporated into genetic counselors' practice in the United States, as well as describe current attitudes and challenges associated with their integration. An electronic survey was sent by email to members of the National Society of Genetic Counselors (NSGC). A total of 325 American Board of Genetic Counselors-certified genetic counselors who provide direct patient care in the United States for at least 50% of their time were included in data analysis. Results showed that the frequency and timing of various insurance- and billing-related tasks were not consistent among respondents, even those practicing in similar settings. Inadequate training to complete tasks was reported by 64% of respondents, and 47% reported a lack of resources from their employer and/or institution to complete genesurance tasks. Additionally, only 38% of respondents agreed that insurance- and billing-related tasks were within the scope of the genetic counseling practice, and there was little consensus on who respondents believe is the most appropriate person to complete these tasks. When asked how genesurance considerations affected job satisfaction, 85% of respondents reported a negative impact. This study found an inconsistent genesurance workflow among genetic counselors practicing in the United States, a lack of consensus on who should be responsible for genesurance tasks, several challenges associated with completing these tasks, and identifies genesurance considerations as potential risk factors for genetic counselor burnout.

Efficacy of a medical genetics rotation during pediatric training.

PURPOSE: With the greater understanding that genetics underlies the basis of health and disease, the practice of medicine is changing such that we are now in an era of genomic medicine. However, there has been a deficiency of training in genetics and genomics among primary care residents. METHODS: We describe the experience of our institution, which requires pediatric, child neurology, and medicine-pediatric residents to complete a subspecialty rotation in medical genetics. Standardized end-of-rotation evaluation results were analyzed and thematic analysis was performed. RESULTS: The mean overall educational quality of the rotation rated on a 5-point scale ranging from 1 (poor) to 5 (excellent) was 4.49. The participation in medical genetics had three main outcomes: (i) a variety of learning opportunities were presented such that it was one of the most educational rotations that trainees experienced; (ii) both trainee competence and confidence in clinical practice improved through knowledge gained; and (iii) an increased awareness and appreciation for interprofessional relationships, especially for the genetic counseling profession, was highly valued. In addition, some residents have gone on to choose medical genetics as a profession. CONCLUSION: A rotation in medical genetics increases knowledge and awareness of the importance that medical genetics has in clinical practice.

Spiritual Exploration in the Prenatal Genetic Counseling Session.

Religion and spirituality (R/S) are important components of many individuals' lives, and spirituality is often employed by women coping with pregnancy complications. To characterize how prenatal genetic counselors might address spiritual issues with patients, 283 English and Spanish speaking women receiving prenatal genetic counseling in Houston, Texas were surveyed post-counseling using both the Brief RCope and questions regarding interest in spiritual exploration. Genetic counselors were concurrently surveyed to identify religious/spiritual language used within sessions and perceived importance of R/S. Genetic counselors were significantly more likely to identify R/S as important to a patient when patients used religious/spiritual language (p < 0.001). Conversely, when no religious/spiritual terms were present, the counselor felt uncertain about the importance of R/S 63 % of the time. However, 67 % of patients reported that they felt comfortable sharing their faith as it relates to their pregnancy, and 93 % reported using positive religious coping. Less than 25 % reported a desire for overt religious actions such as prayer or scripture exploration. Therefore, most patients' desires for spiritual exploration center in the decision making and coping processes that are in line with the genetic counseling scope of practice. Thus, counselors should feel empowered to incorporate spiritual exploration into their patient conversations.

Perceptions of Latinas on the Traditional Prenatal Genetic Counseling Model.

The traditional genetic counseling model encompasses an individualized counseling session that includes the presentation of information about genes, chromosomes, personalized risk assessment, and genetic testing and screening options. Counselors are challenged to balance the provision of enough basic genetic information to ensure clients' understanding of the genetic condition in question with a personalized discussion of what this information means to them. This study explored the perceptions Latinas have about prenatal genetic counseling sessions and aimed to determine if they had preferences about the delivery of care. Data were collected through focus groups and one-on-one, semi-structured interviews of 25 Spanish speaking Latinas who received genetic counseling during their current pregnancy. We implemented grounded theory to evaluate participant responses, and were able to identify common emergent themes. Several themes were identified including an overall satisfaction with their prenatal genetic counseling appointment, desire for a healthy baby, peace of mind following their appointment, lack of desire for invasive testing, and faith in God. Several participants stated a preference for group genetic counseling over the traditional individual genetic counseling model. Our data indicate that Latinas value the information presented at prenatal genetic counseling appointments despite disinterest in pursuing genetic testing or screening and suggest that group prenatal genetic counseling may be an effective alternative to the traditional genetic counseling model in the Latina population.

"I didn't know it existed before you called": protestant clergy experience, education and perceptions regarding genetics.

Despite the intrinsic role religious/spiritual (hereafter, R/S) beliefs have in patient clinical decision-making and crisis coping, there is little research exploring the relationship that exists between clergy (professionals who provide R/S counsel and guidance) and genetic counseling patients. This qualitative, exploratory study was designed to explore Protestant clergy (N = 8) perceptions of and experience with genetics-related issues. Data analysis revealed that a wide range of R/S perceptions regarding genetics-related issues exist within Protestantism, Protestant clergy have a basic understanding of genetic testing and conditions, and while directive counseling is inherent to Protestant clergy counseling, there appears to exist two opposing styles: unbiased and biased. Based on this information, there are two main implications for genetic counseling clinical practice. First, R/S assessments need to be increasingly implemented into genetic counseling sessions, so that the psychosocial needs of patients with specific R/S beliefs can be identified and addressed. An increase in R/S assessments may be accomplished by increased exposure in genetic counselor training, continuing education opportunities, and by establishing relationships with board-certified, professional chaplains. Second, genetic counselors can influence the genetic education and experience of clergy by raising awareness within their own R/S assemblies. Doing so can also serve to further educate genetic counselors in the R/S beliefs of their own traditions, thus increasing sensitivity, empathy and the quality of care provided.