Origins of accessory small ring marker chromosomes derived from chromosome 1.

Three patients with accessory small ring chromosomes derived from chromosome 1 are presented together with additional clinical details and cytogenetic analyses of a previously reported patient. Cytogenetic analysis was undertaken by FISH using a reverse painting probe generated from one of the patients by microdissection of the r(1) chromosome and with a BAC923C6 which maps to 1p12. Results indicated that patients with r(1) chromosomes consisting of 1q12 heterochromatin and short arm pericentric euchromatin which extends to at least the BAC923C6 were associated with a normal or mild phenotype. Patients with abnormal phenotypes possessed two types of rings. One patient had evidence for contiguous pericentric short arm euchromatin which extended from the centromere to beyond the BAC923C6. Two patients showed molecular cytogenetic results which were compatible with non-contiguous chromosome 1 euchromatin. The diversity of origin of r(1)s will hamper attempts to define phenotype/genotype relationships.

Discordant neutrophil alkaline phosphatase activity and cytogenetic response in chronic myeloid leukemia treated with alpha-interferon.

Decreased neutrophil alkaline phosphatase (NAP) synthesis is a classical feature of Philadelphia (Ph) positive chronic phase chronic myeloid leukemia (CML). Whether this aberration is an integral leukemic property of the cell or results from mediation by other factors is unclear. During alpha-interferon (alpha-IFN) based therapy the relationship between Ph chromosome suppression and NAP synthesis was examined. Four categories of response were observed in 19 patients studied sequentially. Significantly, persistent low NAP activity was observed in one patient in complete cytogenetic remission, while a second group of 7 patients demonstrated normal NAP activity in spite of persistence of the Ph chromosome in 100% of metaphases. In the absence of various clinical influences that can modulate NAP activity in chronic phase CML, the results reinforce the observation that the BCR/ABL fusion gene product is not a key factor influencing NAP activity in CML.

Proximal 15q variant with normal phenotype in three unrelated individuals.

Three individuals, ascertained for differing reasons, were found to have extra material in the proximal long arm of chromosome 15. The abnormal offspring of one of these also carried this chromosome. The extra material appears identical in all four individuals. The occurrence of this variant in patients of normal phenotype indicates that the region q11-q13 of chromosome 15 contains material which can be duplicated with little effect, unless the gene whose disruption causes Prader-Willi syndrome is involved at the breakpoint.

Register of chromosomal abnormalities in Queensland.

The development and use of the computer-aided retrieval of karyotypes (CAROK), a register of chromosomal abnormalities in Queensland, is described. The six independent cytogenetic laboratories serving the population of 2.2 million contribute data to the register which provides total population information on the occurrence of chromosomal abnormalities, without selection. CAROK policy on confidentiality, security, access, and safety of data is described in detail. A cytogenetic register such as this ensures a reliable permanent file of results, facilitates research, and provides a data base which will enable questions of clustering or secular trends to be answered efficiently. The register is complete for the years 1976-1981, and contains information on 880 consecutive abnormal cases; in this sense, the data constitute an unselected six-year series of diagnosed chromosomal abnormalities in Queensland. These figures show an average incidence figure (over a six-year period) for newly diagnosed cases of chromosomal abnormality of 6.61/100 000 general population per year.