Detection of mosaicism in amniotic fluid cultures: a CYTO2000 collaborative study.

PURPOSE: To evaluate the assumptions on which the American College of Medical Genetics (ACMG) Standards and Guidelines for detecting mosaicism in amniotic fluid cultures are based. METHODS: Data from 653 cases of amniotic fluid mosaicism were collected from 26 laboratories. A chi-square goodness-of-fit test was used to compare the observed number of mosaic cases with the expected number based on binomial distribution theory. RESULTS: Comparison of observed data from the in situ colony cases with the expected distribution of cases detected based on the binomial distribution did not reveal a significant difference (P = 0.525). CONCLUSIONS: The empirical data fit the binomial distribution. Therefore, binomial theory can be used as an initial discussion point for determining whether ACMG Standards and Guidelines are adequate for detecting mosaicism.

Gene mapping of Usher syndrome type IIa: localization of the gene to a 2.1-cM segment on chromosome 1q41.

Usher syndrome type II is associated with hearing loss and retinitis pigmentosa but not with any vestibular problems. It is known to be genetically heterogeneous, and one locus (termed USH2A) has been linked to chromosome 1q41. In an effort to refine the localization of USH2A, the genetic map of the region between and adjacent to the marker loci previously recognized as flanking USH2A (D1S70 and PPOL) is updated. Analysis of marker data on 68 Usher II families places the USH2A gene into a 2.1-cM region between the markers D1S237 and D1S229. The gene for transforming growth factor beta 2 (TGFB2) and the gene for the homeodomain box (HLX1) are both eliminated as candidates for USH2A, by virtue of their localization outside these flanking markers. The earlier finding of genetic heterogeneity was confirmed in six new families, and the proportion of unlinked Usher II families is estimated at 12.5%. The placement of the USH2A gene into this region will aid in the physical mapping and isolation of the gene itself.

Data collection in the Great Plains Genetics Service Network: using limited funds to collect data from centers with varying resources.

The Data Committee of the Great Plains Genetics Service Network (GPGSN) coordinates the collection of data relating to delivery of genetic services in eight states. These states are Iowa, Missouri, Arkansas, Oklahoma, Kansas, Nebraska, South Dakota and North Dakota. The funds allocated to this project by the GPGSN are limited. The distance between genetics service sites is great and the population density in the regions being served is low. The local resources available to the genetics services sites participating in data collection vary from robust to "bare-bones". The approach to solving the problem involved the following. First the committee the data items to be collected were identified and defined. Second, a standard format for transmitting the data to the GPGSN regional coordinating center in Iowa City was developed. Third, the services sites and their resources for collecting data were identified. Fourth, resources were allocated to different sites in a manner that seemed most able to help that center to contribute data to the regional center. Fifth, data were aggregated at the regional center and aggregated data reports were returned to collecting sites. Finally, items were modified in response to the feedback received from the genetics services sites. Although the philosophy is that data collection should be a by-product of providing quality genetic services, the region recognizes that service sites will need help to conform with regional standards. Therefore the region encourages each service site to develop its own method to collect data, and provides assistance to it in getting the data into the regional transmission format.(ABSTRACT TRUNCATED AT 250 WORDS)

Familial dyslexia: use of genetic linkage data to define subtypes.

Specific reading disability is an example of a complex behavioral disorder which is clinically heterogeneous. It is probably also heterogeneous at the levels of etiology and process (pathogenesis), but there may not be a 1:1:1 mapping of etiology to process to clinical outcome. Thus, classification of cases by clinical features may not lead to discovery of the underlying processes or etiologies, and it may be profitable to define subgroups by etiology. There is evidence for genetic etiology in some cases, but there is genetic heterogeneity as well. Possible genetic models for specific reading disability include polygenic, oligogenic, and single gene inheritance, and there are several types of genetic analysis that can be used to determine which of these modes of inheritance may be present. Identification of individual genes is possible in single gene and oligogenic disorders. Clinical studies and molecular analysis can then be used to determine gene function.

Cat-eye syndrome with different marker chromosomes in a mother and daughter.

Except for atypical eye findings in the daughter, a mother and daughter with bisatellited marker chromosomes had abnormalities consistent with cat-eye syndrome. The mother's marker chromosome (mar number 1) is derived from one 22 and another acrocentric, possibly also a 22; the daughter's marker (mar number 2) may be an iso-dicentric, inv-dup (22) derivative of mar number 1. The mother has a tertiary trisomy translocation chromosome composed of at least one and perhaps two copies of 22pter----q11.2, whereas the daughter clearly has a secondary trisomy 22pter----q11.2 isochromosome, confirming this region as a cause of cat-eye syndrome. Results of hybridization using a unique sequence probe localized to 22q11 are consistent with the interpretation that both ends of both marker chromosomes are derived from 22.

Cytogenetic studies of a patient with mosaicism of isochromosome 13q and a dicentric (Y;13) translocation showing differential centromeric activity.

A case is presented in which both an isochromosome and a dicentric translocation with differential centromere activity are found in one individual. Three karyotypes are present: 46,XY, -13, + i(13q)/45,X, -13, + psu dic(13)t(13;Y)/45,X, -13, + psu dic(Y)t(Y;13). The isochromosome 13q is found in 23% of cells in blood and 5% in skin. The dicentric (Y;13) chromosome in all of the remaining cells displays differential centromeric activity; the ratio of cells with the active 13 centromere to the active Y centromere is about 3.5:1. The formation of the isochromosome 13q was a de novo gametic event. The translocation producing the dicentric occurred after fertilization with the breakpoints at band Yq12 and the juxta-centromeric region of the isochromosome 13. The finding of differential centromeric activity in this chromosome indicates that centromere inactivation is not always permanent in a dicentric translocation.