Evaluating a communication aid for return of genetic results in families with hypertrophic cardiomyopathy: A randomized controlled trial

Introduction: Genetic testing for hypertrophic cardiomyopathy (HCM) is considered a key aspect of management. Communication of genetic test results to the proband and their family members, can be a barrier to effective uptake. We hypothesized that a communication aid would facilitate effective communication, and sought to evaluate knowledge and communication of HCM risk to at-risk relatives. Methods: This was a prospective randomized controlled trial. Consecutive HCM patients attending a specialized clinic, who agreed to participate, were randomized to the intervention or current clinical practice. The intervention consisted of a genetic counselor-led appointment, separate to their clinical cardiology review, and guided by a communication booklet which could be written in and taken home. Current clinical practice was defined as the return of the genetic result by a genetic counselor and cardiologist, often as part of a clinical cardiology review. The primary outcome was the ability and confidence of the individual to communicate genetic results to at-risk relatives. Results: The a priori outcome of improved communication amongst HCM families did not show statistically significant differences between the control and intervention group, though the majority of probands in the intervention group achieved fair communication (n=13/22) and had higher genetic knowledge scores than those in the control group (7 +/- 3 versus 6 +/- 3). A total of 29% of at-risk relatives were not informed of a genetic result in their family. Conclusion: Communication amongst HCM families remains challenging, with nearly a third of at-risk relatives not informed of a genetic result. We show a significant gap in the current approach to supporting family communication about genetics.

Prevalence of Returnable Genetic Results Based on Recognizable Phenotypes among Children with Autism Spectrum Disorder

The importance of extensive genetic testing of autism spectrum disorder (ASD) cases has been demonstrated repeatedly in research settings but such testing in clinical settings remains sporadic. Determining which individuals should be prioritized for expensive tests remains a challenge. Several guidelines have been released relating to clinical genetic evaluations and testing in the context of ASD and these guidelines may be informed by the results of genetic testing in large research cohorts. The current study summarizes findings from over 2,000 individuals with ASD who received genetic testing, including microarray and exome testing, through the Simons Simplex Consortium. A returnable genetic result is identified in 10% of cases, however, this yield increases based on four readily accessible phenotypes: female sex and the presence of intellectual disability, seizures or delayed walking. Combinations of these factors increase return rate further, with some combinations yielding a return rate over 50%. In conclusion, these four phenotypes provide a simple approach to prioritize genetic testing in a clinical setting and inform future clinical guidelines. Providing a systematic approach to decisions about who to test removes barriers for, and therefore decrease disparities in, reimbursable genetic testing for individuals diagnosed with ASD.

Co-occurrence of an HSPG2 Missense Variant and Functional Polymorphisms in Atypical Schwartz–Jampel Syndrome Type 1 with Obesity: A Case Report

Schwartz–Jampel syndrome type 1 (SJS1) is an autosomal recessive chondrodystrophic myotonia, linked to heparan sulfate proteoglycan 2 (HSPG2) variants. We describe a patient with typical features of SJS1, but not obesity. Clinical exome sequencing detected a rare missense variant in HSPG2, confirming our clinical diagnosis, but also two homozygous variants in SDC3 and ADRB3 genes, previously described to be associated with obesity. This additional genetic result could better explain our patient's phenotype. Despite the phenotypic variability associated to HSPG2 variants, it is advisable to carefully check other possible genetic causes underlying clinical signs not strictly related to the classical phenotype of SJS1.

Sediment preference, salinity tolerance and COX-1 genetic differences in two purportive species of Luidia (Echinodermata: Asteroidea)

Specimens collected in or near Pensacola Bay, Florida matching the descriptions of Luidia lawrencei and Luidia clathrata (the congener from which L. lawrencei was recently split) were compared to determine whether their recent taxonomic separation is supported by differences in sediment preference, salinity tolerance and COX-1 mtDNA sequences. Luidia clathrata has a preference for smaller grain sizes, while no statistically significant preference was found for Luidia lawrencei, and no significant difference was found between the species. Luidia clathrata is more tolerant of lower salinity based on the righting response than Luidia lawrencei, especially at salinities lower than 25 g kg−1. The COX-1 comparison returned over 99% homology among individuals of the two species. While sediment preference and salinity tolerance results indicate differences in response to habitat dissimilarities, the COX-1 genetic result is strong evidence against the recently proposed separation of the species. In light of the COX-1 result, we interpret the sediment and salinity results as long-term acclimation responses.

Genetic Diagnosis of Factor V Leiden Using Heteroduplex Technology

SummaryA new genetic test has been developed for detection of the mutation known as factor V Leiden. The test employs heteroduplex technology and comprises a single PCR reaction followed immediately by PCR product analysis. It therefore represents the minimum practical route from blood/tissue sample to genetic result. A cohort of 100 patients with a history of thrombosis have been screened using both the new heteroduplex test and a previously described PCR-restriction endonuclease test. Results gave 100% correlation: normals 75 (75%), heterozygotes 24 (24%) and homozygotes 1 (1%). The heteroduplex test has been shown to give straightforward diagnosis in three different analytical systems: standard polyacrylamide gel electrophoresis (PAGE), mini-gel PAGE and capillary electrophoresis. The latter system is semiautomated, therefore rapid through-put of large sample numbers is now · possible.