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Complete Ascertainment (complete + ascertainment)
Selected AbstractsComplete ascertainment of intragenic copy number mutations (CNMs) in the CFTR gene and its implications for CNM formation at other autosomal loci,HUMAN MUTATION, Issue 4 2010Sylvia Quemener Abstract Over the last 20 years since the discovery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, more than 1,600 different putatively pathological CFTR mutations have been identified. Until now, however, copy number mutations (CNMs) involving the CFTR gene have not been methodically analyzed, resulting almost certainly in the underascertainment of CFTR gene duplications compared with deletions. Here, high-resolution array comparative genomic hybridization (averaging one interrogating probe every 95,bp) was used to analyze the entire length of the CFTR gene (189,kb) in 233 cystic fibrosis chromosomes lacking conventional mutations. We succeeded in identifying five duplication CNMs that would otherwise have been refractory to analysis. Based upon findings from this and other studies, we propose that deletion and duplication CNMs in the human autosomal genome are likely to be generated in the proportion of approximately 2,3:1. We further postulate that intragenic gene duplication CNMs in other disease loci may have been routinely underascertained. Finally, our analysis of ±20,bp flanking each of the 40 CFTR breakpoints characterized at the DNA sequence level provide support for the emerging concept that non-B DNA conformations in combination with specific sequence motifs predispose to both recurring and nonrecurring genomic rearrangements. Hum Mutat 31:1,8, 2010. © 2010 Wiley-Liss, Inc. [source] Ascertainment of birth defects: The effect on completeness of adding a new source of dataJOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 6 2000C Bower Background: The Western Australian (WA) Birth Defects Registry aims for complete ascertainment of birth defects in WA, but the proportions of birth defects in rural areas and in Aboriginal children are lower than in metropolitan and non-Aboriginal children. The effect on ascertainment of adding data from the Rural Paediatric Service (RPS) was investigated. Method: A file of all cases of birth defects for children born 1980,1997 and recorded on the RPS database was linked to the Registry. Results: The addition of this new data source had little effect on the overall prevalence of birth defects (an increase from 5.38 to 5.41%). There was a slightly greater effect on the prevalence of birth defects in rural residents (4.67%,4.76%) and Aboriginal children (4.55,4.78%), although the prevalence for each of these groups is still less than for metropolitan residents and non-Aboriginal infants, respectively. All major categories of birth defects were represented in the new cases and, in general, their addition made little difference to the prevalence of each category. The exception was fetal alcohol syndrome, which increased from 0.13 per 1000 to 0.18 per 1000 once the 21 new cases from the RPS were added. Conclusion: Complete ascertainment of birth defects is important in developing and evaluating preventive programs, and in investigating clusters of birth defects. [source] Congenital malformations in infants whose mothers reported the use of folic acid in early pregnancy in Sweden.CONGENITAL ANOMALIES, Issue 4 2007A prospective population study ABSTRACT The use of folic acid prior to conception is generally recommended for the prevention of birth defects, notably neural tube defects. In a previous study from Sweden, based on interviews of women in early pregnancy, no such effect was found on the general malformation rate, but data for neural tube defects were scarce. Using data from the Swedish Medical Birth Register for the years 1995,2004, 20 891 women were identified who reported the use of folic acid in early pregnancy, but not of anticonvulsants. These women were compared to all other women who gave birth during the study period. Malformations in the infants born were identified from multiple sources. No reduction in the general malformation rate was seen among infants born to women who reported the use of folic acid (OR = 1.09, 95% CI 1.02,1.17) and no effect of neural tube defect rate was seen (RR = 1.35, 95% CI 0.82,2.22), based on 16 infants with neural tube defect whose mother reported the use of folic acid. No effect was seen on the rates of other malformations except for cardiac defects, where a statistically significant increased risk (notably for severe defects) was found (OR = 1.19, 95% CI 1.05,1.35). The effect of various deficiencies in data collection is discussed, but is unlikely to explain the lack of protective effect noticed. So far, it has not been possible to demonstrate a beneficial effect of folic acid supplementation on malformation risk in Sweden. A more complete ascertainment and detailed timing and dosage of folic acid use in a prospective study is recommended. [source] The estimation of sibling genetic risk parameters revisitedGENETIC EPIDEMIOLOGY, Issue 4 2004Guohua Zou Abstract This report points out that some sibling genetic risk parameters can be regarded as the ratios of the characteristic values in the ascertainment subpopulation. Based on this observation, we reconsider Olson and Cordell's ([2000] Genet. Epidemiol. 18:217,235) and Cordell and Olson's ([2000] Genet. Epidemiol. 18:307,321) estimators, and re-derive these estimators. Furthermore, we provide the closed-form variance estimators. Simulation results suggest that our proposed estimators perform very well, and single ascertainment may be better than complete ascertainment for estimating these genetic parameters. © 2004 Wiley-Liss, Inc. [source] Incidence of Hip and Other Osteoporotic Fractures in Elderly Men and Women: Dubbo Osteoporosis Epidemiology Study,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2004Kevin P Chang Abstract In this prospective 12-year study in men and women 60 years of age and older, there was a 4,6% per year reduction in the incidence rate of overall osteoporotic fractures, but the study was unable to exclude any change in the hip fracture incidence rate. Approximately one-half of hip fractures occurred before 80 years in men and two-thirds before 85 years in women. The age distribution of hip fractures underlines the need for earlier intervention in osteoporosis. Introduction: Although hip fracture is the major osteoporotic fracture in terms of health outcomes, quality of life, and costs, there is a paucity of long-term data on secular changes in men and women within a defined community. This long-term prospective population-based study over 12 years from 1989 to 2000 specifically examined the age distribution and secular changes in the incidence rates of hip and other osteoporotic fractures in men and women 60 years of age and older in a predominantly white population in Dubbo, Australia. Materials and Methods: Hip and all other clinical fractures were ascertained by reviewing all radiography reports from the two area radiology services, ensuring complete ascertainment of all clinical osteoporotic fractures. Results and Conclusion: Among the 1055 symptomatic atraumatic fractures (after excluding pathological fractures), there was a significant reduction in the overall fracture incidence rate in women (4% per year; p = 0.0003) and men (6% per year; p = 0.0004) over the 12 years. There were 229 hip fractures (175 in women and 54 in men) within 39,357 person-years of observation. The overall rate ± SE of hip fracture was 759 ± 57 per 100,000 person-years in women and 329 ± 45 per 100,000 person-years in men, with an exponential increase with age. With advancing age, the incidence rate of hip fractures in men approached that in women; the female:male ratio fell from 4.5 (95% CI: 1.3,15.7) to 1.5 (0.9,2.5) and 1.9 (1.2,2.8) in the 60,69, 70,79, and 80+ year age groups, respectively. In women, the absolute number of fractures and incidence rate continuously increased with age; however, in men, the absolute number of hip fractures peaked at 80,84 years of age and then decreased. Most importantly, despite the continuing increase with age, almost one-half (48%) of the hip fractures occurred before the age of 80 years in men, and 66% of hip fractures occurred before the age of 85 years in women. The overall hip fracture incidence is comparable with other white (except Sweden) and Asian groups as well as two other Australian studies. This study could not exclude a change in hip fracture incidence rate, even in those 80 years of age and over among whom the incidence of hip fractures was the highest. The incidence data highlight the fact that a large proportion of hip fractures occurs in those under 80 years of age, particularly in men. This age distribution underlines the need for earlier intervention in osteoporosis in women and particularly in men to achieve the most cost-effective outcomes. [source] Ascertainment of birth defects: The effect on completeness of adding a new source of dataJOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 6 2000C Bower Background: The Western Australian (WA) Birth Defects Registry aims for complete ascertainment of birth defects in WA, but the proportions of birth defects in rural areas and in Aboriginal children are lower than in metropolitan and non-Aboriginal children. The effect on ascertainment of adding data from the Rural Paediatric Service (RPS) was investigated. Method: A file of all cases of birth defects for children born 1980,1997 and recorded on the RPS database was linked to the Registry. Results: The addition of this new data source had little effect on the overall prevalence of birth defects (an increase from 5.38 to 5.41%). There was a slightly greater effect on the prevalence of birth defects in rural residents (4.67%,4.76%) and Aboriginal children (4.55,4.78%), although the prevalence for each of these groups is still less than for metropolitan residents and non-Aboriginal infants, respectively. All major categories of birth defects were represented in the new cases and, in general, their addition made little difference to the prevalence of each category. The exception was fetal alcohol syndrome, which increased from 0.13 per 1000 to 0.18 per 1000 once the 21 new cases from the RPS were added. Conclusion: Complete ascertainment of birth defects is important in developing and evaluating preventive programs, and in investigating clusters of birth defects. [source] Familial essential tremor with apparent autosomal dominant inheritance: Should we also consider other inheritance modes?MOVEMENT DISORDERS, Issue 9 2006Shaochun Ma MD Abstract A positive family history is present in many patients with essential tremor (ET), but twin studies and segregation analysis have suggested that ET is not entirely a genetic disorder. Two genetic loci have been identified in autosomal dominant (AD) ET and polymorphisms in the DRD3 and HS1-BP3 genes have been proposed as the possible susceptibility factors for ET. There is also evidence for further genetic heterogeneity. We evaluated 4 unrelated large kindreds with ET with an apparent AD mode of transmission. Each kindred spanned at least 3 generations and contained at least 13 living affected subjects who met criteria for definitive ET. None of the pedigrees had evidence for inheritance of ET from both parents. Known genetic ET loci were excluded in these families. We detected a preferential transmission of ET in every kindred and the proportion of affected offspring varied from 75% to 90% (P < 0.05) in the generations with complete ascertainment. Our data indicate that non-Mendelian preferential transmission of an affected allele is a feature in many ET kindreds with multiple affected members and an apparent AD mode of inheritance. ET may have a complex etiology. Additional genetic models need to be considered, including an interaction of susceptibility genes and environmental risk factors. © 2006 Movement Disorder Society [source] Prevalence study of primary dystonia in IcelandMOVEMENT DISORDERS, Issue 3 2006Hilmir Asgeirsson STUD MED Abstract In Iceland, the crude prevalence for all types of primary dystonia was 37.1/105 (confidence interval, 30.4,44.9). Focal dystonia had the highest prevalence (31.2/105), followed by segmental (3.1/105), multifocal (2.4/105) and generalized dystonia (0.3/105). Cervical dystonia was the most common focal dystonia (11.5/105), followed by limb dystonia (8.0/105), laryngeal dystonia (5.9/105), blepharospasm (3.1/105), and oromandibular dystonia (2.8/105). The male:female ratio for all patients was 1:1.9 (P = 0.0007), and females outnumbered males in all subtypes except oromandibular dystonia. Mean age of onset for all patients was 42.7 years (range, 3,82 years). This prevalence of primary dystonia is higher than in most reported studies, possibly because of more complete ascertainment but the relative frequencies of dystonia subtypes is similar. © 2005 Movement Disorder Society [source] | |||||||||||||