Evaluating the model of offering expanded genetic carrier screening to high school students within the Sydney Jewish community.

Programs offering reproductive genetic carrier screening (RGCS) to high school students within the Ashkenazi Jewish community in several countries including Canada and Australia have demonstrated high uptake and retention of educational messages over time. This study was undertaken to evaluate whether testing for an expanded number of conditions in a high school setting would impact the effectiveness of education. In this questionnaire-based study, genetic carrier testing for nine conditions was offered to 322 year 11 students from five high schools, with students attending a compulsory 1-h education session prior to voluntary testing. Comparison of pre- and post-education measures demonstrated a significant increase in knowledge, positive attitudes, and reduced concern immediately after the education session. Retention of knowledge, measures of positive attitude, and low concern over a 12-month period were significantly higher than baseline, although there was some reduction over time. In total, 77% of students exhibited informed choice regarding their intention to test. A significant increase in baseline knowledge scores and positive attitude was also demonstrated between our original 1995 evaluation (with testing for only one condition) and 2014 (testing for nine conditions) suggesting community awareness and attitudes to RGCS have increased. These findings validate the implementation of effective education programs as a key component of RGCS and are relevant as gene panels expand with the introduction of genomic technologies.

Intrafamilial Phenotypic Variability in the C9orf72 Gene Expansion: 2 Case Studies.

The C9orf72 genetic mutation is the most common cause of familial frontotemporal dementia (FTD) and motor neuron disease (MND). Previous family studies suggest that while some common clinical features may distinguish gene carriers from sporadic patients, the clinical features, age of onset and disease progression vary considerably in affected patients. Whilst disease presentations may vary across families, age at disease onset appears to be relatively uniform within each family. Here, we report two individuals with a C9orf72 repeat expansion from two generations of the same family with markedly different age at disease onset, clinical presentation and disease progression: one who developed motor neuron and behavioural symptoms in their mid 40s and died 3 years later with confirmed TDP-43 pathology and MND; and a second who developed cognitive and mild behavioural symptoms in their mid 70s and 8 years later remains alive with only slow deterioration. This report highlights the phenotypic variability, including age of onset, within a family with the C9orf72 repeat expansion.