Mutations in the retinal guanylate cyclase (RETGC-1) gene in dominant cone-rod dystrophy

The dominant cone-rod dystrophy gene CORD6 has previously been mapped to within an 8 cM interval on chromosome 17p12-p13. The retinal- specific guanylate cyclase gene (RETGC-1), which maps to within this genetic interval and previously was implicated in Leber's congenital amaurosis, was screened for mutations within this family and in a panel of small families and individuals with various cone and cone- rod dystrophy phenotypes. A missense mutation (E837D) was identified in affected members of the CORD6 family, as well as a second missense mutation (R838C) in three other families with dominant cone-rod dystrophy. RETGC-1 is only the fourth gene to be implicated in cone-rod dystrophy and this is the first report of dominant mutations in this gene.      

Localization of a gene for otosclerosis to chromosome 15q25-q26

Among white adults otosclerosis is the single most common cause of hearing impairment. Although the genetics of this disease are controversial, the majority of studies indicate autosomal dominant inheritance with reduced penetrance. We studied a large multi- generational family in which otosclerosis has been inherited in an autosomal dominant pattern. Five of16 affected persons have surgically confirmed otosclerosis; the remaining nine have a conductive hearing loss but have not undergone corrective surgery. To locate the disease- causing gene we completed genetic linkage analysis using short tandem repeat polymorphisms (STRPs) distributed over the entire genome. Multipoint linkage analysis showed that only one genomic region, on chromosome 15q, generated a lod score >2.0. Additional STRPs were typed in this area, resulting in a lod score of 3.4. STRPs FES (centromeric) and D15S657 (telomeric) flank the 14. 5 cM region that contains an otosclerosis gene.      

P67L: a cystic fibrosis allele with mild effects found at high frequency in the Scottish population.

Only three mutant cystic fibrosis (CF) alleles have to date been established as conferring a dominant mild effect on affected subjects who are compound heterozygotes. We now add a fourth, P67L, which occurs on about 1.4% of Scottish CF chromosomes. Among 13 patients (12 unrelated) with this allele, the average age at diagnosis was 22.5 +/- 11.3 years. None of the cases had consistently raised sweat chloride concentrations, the average value being 57 +/- 9 mmol/l; 77% of the patients were pancreatic sufficient. When compared to three other established mild CF alleles, R117H, A455E, and 3849 + 10kb C-T, a compound heterozygote for P67L has minimal disease and clinical suspicions are unlikely to be confirmed other than by DNA typing.     

Contraceptive potential of a mifepristone-nomegestrol acetate sequential regimen in women

The effectiveness of a sequential regimen consisting of mifepristone, 10 mg/day for 15 days, followed by nomegestrol acetate (NOMA), 5 mg/day for the next 13 days, for inhibiting ovulation and maintaining regular bleeding cycles was assessed in 10 surgically sterilized volunteers who were followed for one pretreatment and three treated cycles. Hormonal determinations in blood and urine, ovarian ultrasonography, bleeding records in all cycles and an endometrial biopsy taken on day 22-25 of the third treatment cycle were used to monitor the effects of treatment. During treatment, 24 monophasic (no sustained progesterone rise above 12 nmol/l) and six biphasic cycles were recorded. Nine follicular ruptures were detected echographically in these 30 treated cycles, five of which occurred in monophasic cycles. All follicular ruptures occurred on days 1-7 of NOMA treatment. Echographic and endocrine features of ovulatory cycles were both present in only four treated cycles (13.3%). Development of a secretory endometrium was achieved in all cases, but it was always irregular. Regular withdrawal bleeding occurred in all subjects and no adverse reactions were recorded. The ovarian and endometrial effects of this regimen justify testing its contraceptive effectiveness in phase 2 clinical trials.      

Neurosurgical anatomy of the anterior interhemispheric approach for aneurysms of the anterior communicating artery (26.6.92)

Summary The anterior interhemispheric approach for aneurysms of the anterior communicating artery was studied in ten cadavers. This approach presents several advantages over the pterional approach widely used in neurosurgery. It allows direct access to the region of the anterior communicating artery complex with minimal retraction of the brain and preservatioin of the olfactory tract and the gyrus rectus.

---

Bases anatomiques de l'abord inter-hémisphérique antérieur lors de la chirurgie des anévrysmes de l'artère communicante antérieure

Résumé Ce travail concerne l'abord neurochirurgical des anévrysmes de l'artére communicante antérieure par voie frontale interhémisphérique. L'étude anatomique a été réalisée sur dix sujets. Cette exposition possède de nombreux avantages comparée à la voie ptérionale habituelle : voie d'abord reduite médiane permettant une visualisation directe et symétrique du complexe artériel de l'artére communicante antérieure ; avec le moindre manipulation et retraction du cerveau en respectant les voies olfactives et le gyrus rectus.