METHODS: In 14 Central England general practices, a novel case-finding tool (Familial Hypercholetserolaemia Case Ascertainment Tool, FAMCAT1) was applied to the electronic health records of 86 219 patients with cholesterol readings (44.5% of total practices' population), identifying 3375 at increased risk of FH. Of these, a cohort of 336 consenting to completing Family History Questionnaire and detailed review of their clinical data, were offered FH genetic testing in primary care.
RESULTS: Genetic testing was completed by 283 patients, newly identifying 16 with genetically confirmed FH and 10 with variants of unknown significance. All 26 (9%) were recommended for referral and 19 attended specialist assessment. In a further 153 (54%) patients, the test suggested polygenic hypercholesterolaemia who were managed in primary care. Total cholesterol and low-density lipoprotein-cholesterol levels were higher in those patients with FH-causing variants than those with other genetic test results (p=0.010 and p=0.002).
CONCLUSION: Electronic case-finding and genetic testing in primary care could improve identification of FH; and the better targeting of patients for specialist assessment. A significant proportion of patients identified at risk of FH are likely to have polygenic hypercholesterolaemia. There needs to be a clearer management plan for these individuals in primary care.
TRIAL REGISTRATION NUMBER: NCT03934320.
METHODS: Seven hundered fifty five individuals from specialist clinics and community health screenings with LDL-c level ≥ 4.0 mmol/L were selected and diagnosed as FH using the DLCC, the SB Register criteria, the US MEDPED and the JFHMC. The sensitivity, specificity, efficiency, positive and negative predictive values of individuals screened with the SB register criteria, US MEDPED and JFHMC were assessed against the DLCC.
RESULTS: We found the SB register criteria identified more individuals with FH compared to the US MEDPED and the JFHMC (212 vs. 105 vs. 195; p
CONCLUSION: All mutations are private except one mutation; p.Ile1254Phe was found in three unrelated families. Identification of a recurrent p.Ile1254Phe mutation suggests the presence of a common and unique mutation in our population. Our study also expands the mutational spectrum of the CPS1 gene.
CASE PRESENTATION: This is a rare case of a pair of 8-year-old monochorionic diamniotic identical twin, who on family cascade screening were diagnosed as definite FH, according to the Dutch Lipid Clinic Criteria (DLCC) with a score of 10. There were no lipid stigmata noted. Baseline lipid profiles revealed severe hypercholesterolaemia, (TC = 10.5 mmol/L, 10.6 mmol/L; LDL-c = 8.8 mmol/L, 8.6 mmol/L respectively). Their father is the index case who initially presented with premature CAD, and subsequently diagnosed as FH. Family cascade screening identified clinical FH in other family members including their paternal grandfather who also had premature CAD, and another elder brother, aged 10 years. Genetic analysis by targeted next-generation sequencing using MiSeq platform (Illumina) was performed to detect mutations in LDLR, APOB100, PCSK9, ABCG5, ABCG8, APOE and LDLRAP1 genes. Results revealed that the twin, their elder brother, father and grandfather are heterozygous for a missense mutation (c.530C > T) in LDLR that was previously reported as a pathogenic mutation. In addition, the twin has heterozygous ABCG8 gene mutation (c.55G > C). Their eldest brother aged 12 years and their mother both had normal lipid profiles with absence of LDLR gene mutation.
CONCLUSION: A rare case of Asian monochorionic diamniotic identical twin, with clinically diagnosed and molecularly confirmed heterozygous FH, due to LDLR and ABCG8 gene mutations have been reported. Childhood FH may not present with the classical physical manifestations including the pathognomonic lipid stigmata as in adults. Therefore, childhood FH can be diagnosed early using a combination of clinical criteria and molecular analyses.
METHODS: We conducted focus groups among healthy English-speaking Malay women in Singapore, aged 40 to 69 years, using a structured guide developed through literature review, expertise input and participant refinement. Thematic analysis was conducted to extract dominant themes representing key motivators and barriers to screening and genetic testing. We used grounded theory to interpret results and derive a framework of understanding, with implications for improving uptake of services.
RESULTS: Five focus groups (four to six participants per group) comprising 27 women were conducted to theme saturation. Major themes were (a) spiritual and religious beliefs act as barriers towards uptake of screening and genetic testing; (b) preference for traditional medicine competes with Western medicine recommendations; (c) family and community influence health-related decisions, complexed by differences in intergenerational beliefs creating contrasting attitudes towards screening and prevention.
CONCLUSIONS: Decisions to participate in breast cancer screening and genetic testing are influenced by cultural, traditional, spiritual/religious, and intergenerational beliefs. Strategies to increase uptake should include acknowledgement and integration of these beliefs into counseling and education and collaboration with key influential Malay stakeholders and leaders.