Genetic discrimination by insurance companies in Aotearoa New Zealand: experiences and views of health professionals.

AIMS: Genetic discrimination in insurance is a significant clinical, research and consumer issue. Recently, the Australian life insurance industry introduced a partial moratorium on the use of genetic test results. However, in Aotearoa New Zealand, both life and health insurers can still use genetic results legally to discriminate against applicants. We aimed to document experiences and concerns of New Zealand-based health professionals (HPs) around the potential misuse of genetic test results for insurance purposes. METHODS: We administered an online survey to New Zealand HPs who discuss genetic testing with patients, their experiences regarding the use of genetic test results in insurance and views on regulation. RESULTS: Twenty-three New Zealand HPs responded, 15 of whom worked in genetics clinics, representing >60% of the total New Zealand clinical genetics workforce. Eleven respondents reported having patients who experienced adverse outcomes related to insurance based on genetic results. Respondents reported patients sometimes/often delayed (n=11) or refused (n=4) genetic testing due to insurance concerns. Over 80% of those who answered (n=17/21) believe insurers' use of genetic results should be legally regulated. CONCLUSION: New Zealand HPs have concerns about insurance companies using genetic test results in underwriting, including the effect on patients, and strongly believe government legislation is required.

Comparative study of microRNA regulation on FOXL2 between adult-type and juvenile-type granulosa cell tumours in vitro.

OBJECTIVES: Despite their distinct biology, granulosa cell tumours (GCTs) are treated similarly to other ovarian tumours. Predominantly expressed in granulosa cells, the transcription factor Forkhead Box L2 (FOXL2) is near absent in juvenile-type GCTs. This research aimed to investigate miRNAs as a mechanism of suppression of FOXL2 expression in juvenile-type GCTs. METHODS: The miRNA abundance of two GCT cell lines COV434 and KGN was profiled using Affymetrix miRNA GeneChip arrays. Luciferase assays were used to confirm miRNA binding to the 3'UTR of FOXL2. Identified as promising candidates, the miR-17 miRNA family was targeted for knockdown with a miRNA sponge. Additionally, individual family members miR-17, miR-20b and miR-106a were knocked down using Anti-miR™ inhibitors. Subsequently, FOXL2 expression was analysed using RT-qPCR and Western blotting. RESULTS: The profiling of COV434 and KGN cells revealed unique miRNA signatures, with COV434 expressing miR-17 family miRNAs whilst KGN expressed members of the let-7 miRNA gene family. Luciferase assays confirmed miRNA binding to FOXL2's 3'UTR. Reduction of miR-17 family miRNAs increased FOXL2 mRNA expression, however luciferase assays performed in combination with the sponge suggested this is an indirect effect. As no changes in protein were observed, we propose another miRNA is repressing the translation of FOXL2 mRNA. CONCLUSION: Through miRNA profiling we have begun to unravel the profiles of GCTs, showing that juvenile and adult derived-cell lines are biologically distinct. By expanding on this discovery we may further elucidate the miRNA-mRNA pathways involved in GCT initiation and progression with potential for novel therapeutics for these cancers.

Brugada syndrome masquerading as febrile seizures.

Fever can precipitate ventricular tachycardia in adults with Brugada syndrome, but such a link has not been reported in children. A 21-month-old white girl presented repeatedly with decreased conscious level and seizures during fever. During a typical episode, rapid ventricular tachycardia was documented. The resting 12-lead electrocardiogram revealed a Brugada electrocardiogram signature. Resting electrocardiograms of the asymptomatic brother and mother were normal, but fever in the mother and pharmacologic stress with ajmaline in the brother revealed Brugada electrocardiogram features. Genetic testing revealed an SCN5A mutation in the affected family members.