Modeling lay people's ethical views on abortion: A Q-methodology study.

BACKGROUND: It isn't clear how lay people balance the various ethical interests when addressing medical issues. We explored lay people's ethical resolution models in relation to abortion. METHODS: In a tertiary healthcare setting, 196 respondents rank-ordered 42 opinion-statements on abortion following a 9-category symmetrical distribution. Statements' scores were analyzed by averaging-analysis and Q-methodology. RESULTS: Respondents' mean (SD) age was 34.5(10.5) years, 53% were women, 68% Muslims (31% Christians), 28% Saudis (26% Filipinos), and 38% healthcare-related. The most-agreeable statements were "Acceptable if health-benefit to woman large," "Acceptable if congenital disease risk large," and "Woman's right if fetus has congenital disease." The most-disagreeable statements were "State's right even if woman disagrees," "Acceptable even with no congenital disease risk," and "Father's right even if woman disagrees." Q-methodology identified several resolution models that were multi-principled, consequentialism-dominated, and associated with respondents' demographics. The majority of Christian women and men identified with and supported a relatively "fetus rights plus State authority-oriented" model. The majority of Muslim women and men identified with and supported a "conception-oriented" model and "consequentialism plus virtue-oriented" model, respectively. One or more of three motives-related statements received extreme ranks on averaging-analysis and in 33% of the models. CONCLUSIONS: 1) On average, consequentialism, focusing on a woman's health-benefit and congenital disease risk, was the predominant approach. This was followed by the rights approach, favoring a woman's interest but taking context into account. 2) Q-methodology identified various ethical resolution models that were multi-principled and partially associated with respondents' demographics. 3) Motives were important to some respondents, providing empirical evidence against adequacy of principlism.

Accelerating novel candidate gene discovery in neurogenetic disorders via whole-exome sequencing of prescreened multiplex consanguineous families.

Our knowledge of disease genes in neurological disorders is incomplete. With the aim of closing this gap, we performed whole-exome sequencing on 143 multiplex consanguineous families in whom known disease genes had been excluded by autozygosity mapping and candidate gene analysis. This prescreening step led to the identification of 69 recessive genes not previously associated with disease, of which 33 are here described (SPDL1, TUBA3E, INO80, NID1, TSEN15, DMBX1, CLHC1, C12orf4, WDR93, ST7, MATN4, SEC24D, PCDHB4, PTPN23, TAF6, TBCK, FAM177A1, KIAA1109, MTSS1L, XIRP1, KCTD3, CHAF1B, ARV1, ISCA2, PTRH2, GEMIN4, MYOCD, PDPR, DPH1, NUP107, TMEM92, EPB41L4A, and FAM120AOS). We also encountered instances in which the phenotype departed significantly from the established clinical presentation of a known disease gene. Overall, a likely causal mutation was identified in >73% of our cases. This study contributes to the global effort toward a full compendium of disease genes affecting brain function.

Molecular characterization of a novel p.R118C mutation in the insulin receptor gene from patients with severe insulin resistance.

CONTEXT: Mutations of the insulin receptor gene (INSR) can cause genetic syndromes associated with severe insulin resistance. OBJECTIVES: We aimed to analyse INSR mutations in Saudi patients with severe insulin resistance. DESIGN: Ten patients with Type A insulin resistance syndrome from five unrelated Saudi families were investigated. The entire coding region of INSR was sequenced. The founder effect was assessed by microsatellite haplotype analysis. The functional effect of the mutation was investigated by in vitro functional assays. RESULTS: A novel biallelic c.433 C>T (p.R118C) mutation was detected in all patients. The c.433 C>T (p.R118C) sequence variation was not found in 100 population controls. The arginine residue at position 118 is located in the ligand-binding domain of INSR and is highly conserved across species. Microsatellite haplotype analysis of these patients indicated that p.R118C was a founder mutation created approximately 2900 years ago. The wild-type and mutant (R118C) INSR were cloned and expressed in CHO cells for functional analysis. Specific insulin binding to the mutant receptor was reduced by 83% as compared to wild-type (WT), although the mutant receptor was processed and expressed on the cell surface. Insulin-mediated receptor autophosphorylation was also significantly reduced in CHO(R118C) cells. CONCLUSIONS: Biallelic c.433 C>T (p.R118C) mutation of INSR causes significant damage to insulin binding and insulin-mediated signal transduction. p.R118C is a founder mutation frequently present in the Saudi patients with severe insulin resistance.