Effects of hyperoxia and caffeine on the expression of fragile site at Xq27.3.

To enhance the cytogenetic expression of the fragile X chromosome, we studied the effects of hyperoxia and caffeine on the induction of fragile Xq27.3. A lymphoblastoid cell line (GM 06912) derived from a fragile X male proband was cultured in RPMI 1640 containing 16% dialyzed fetal calf serum. The cells were synchronously subjected to one of 3 different atmospheric oxygen tensions (21%, 21.3 kPa, normoxic; 40%, 40.5 kPa, hyperoxic; or 60%, 60.8 kPa, hyperoxic) during the last 24 hours of the 72 hour culture, immediately after the addition of 2'-deoxy-5-fluorouridine (FUdR) at 25 ng/ml. To study the enhancing effect of caffeine, with or without hyperoxia, a second set of cultures was additionally subjected to caffeine (2.5 mM) during the last 6 hours of the culture. When the fragility of hyperoxic cells (38.1 kPa dissolved oxygen) was compared to that of normoxic control cells (13.3 kPa dissolved oxygen), the difference was significant (P < 0.05). These data suggest that there is a mean increase in the fragile Xq27.3 expressivity as the dissolved oxygen tension increases. Additionally, we observed that caffeine, with or without hyperoxia, significantly (P < 0.05) suppressed the expression of the fragile X site in this lymphoblastoid cell line.

Constitutional heteromorphism of 9q13 --> q21 in a patient with chronic myelogenous leukemia.

Cytogenetic studies were carried out in a 44-year-old white male because of newly diagnosed chronic myelogenous leukemia. His initial bone marrow study revealed 46,XY, var(9)(q13 -->q21)/46,XY,var(9) (q13-->q21), t(9;22)(q34;q11) karyotypes and later he also acquired a 47,XY,+8,var(9)(q13-->q21), t(9;22)(q34;q11) clone. The var(9)(q13-->q21) heteromorphism was observed in the normal 9 homolog, in 200 GTG-banded bone marrow metaphases in seven cytogenetic studies (1988-90). This heteromorphism was observed in the normal cell line, in the two chronic myelogenous leukemia-related clones, as well as in 100 mitogen-induced peripheral blood lymphocytes, indicating its constitutional nature. This seems to be the first report of var(9)(q13 --> q21) heteromorphism, involving GTG-positive euchromatic band, in a chronic myelogenous leukemia proband.

Trisomy 13: a new recurring chromosome abnormality in acute leukemia.

A new recurring chromosome abnormality was identified in 8 of 621 consecutive successfully karyotyped adults with de novo acute leukemia. These eight patients had trisomy 13 as the sole cytogenetic abnormality. On central morphologic review, five cases were classified as subtypes of acute myeloid leukemia, one as acute mixed lymphoid and myeloid leukemia, one as acute lymphoid leukemia, and one as acute undifferentiated leukemia. Blasts of all eight cases expressed one or more myeloid differentiation antigens. Three also expressed T-lineage-associated antigens; however, none of these had rearrangement of the T-cell receptor beta, gamma, or delta genes. Four of six cases tested were TdT positive. All eight patients with trisomy 13 were treated with intensive induction chemotherapy; only three entered a short-lived complete remission. Survival of patients with trisomy 13 ranged from 0.5 to 14.7 months, and was significantly shorter than that of the remaining patients (median 9.5 v 16.2 months, P = .007). We conclude that trisomy 13 is a rare, recurring clonal chromosome abnormality in acute leukemia associated with a poor prognosis. Malignant transformation of an immature hematopoietic precursor cell is suggested by the expression of antigens characteristic of both the myeloid and lymphoid lineage, the high incidence of TdT positivity, and the morphologic heterogeneity in these leukemias.

Aortic root dilatation associated with partial trisomy 7(q31.2----qter).

Aortic root dilatation and mitral valve prolapse are cardiac findings sometimes seen in disorders of connective tissue, most often in the Marfan syndrome. This report describes an infant with these cardiac anomalies and a specific chromosomal abnormality, partial trisomy of chromosome 7 associated with partial monosomy of chromosome 22. This association may have significance with respect to the etiology of cardiac disease in connective tissue disorders such as Marfan syndrome.

Acute myelomonocytic leukemia (M-4 subtype) with abnormal marrow eosinophilia and a normal chromosome 16.

A variety of chromosome 16 abnormalities, including inversion, deletion, and translocation in patients with acute myelomonocytic leukemia and abnormal marrow eosinophilia have been reported recently. The authors have identified an AMML patient who had a normal karyotype in 50 metaphases. In particular, chromosome 16 was closely examined for abnormality and was found to be entirely normal. In addition, the authors describe new cytochemical and ultrastructural features of the associated abnormal eosinophils.

Focal dermal hypoplasia.

A case of focal dermal hypoplasia (FDH) or Goltz syndrome is described. The patient is a black female infant whose syndrome was first diagnosed at birth. This is a disorder of the mesoectoderm which is manifested by pigmentary skin changes similar to other disease entities, eg, incontinentia pigmenti and Rothmund-Thomson disease, but it is easily confirmed by specific significant histologic findings. The characteristic features are all noted in this infant throughout her follow-up, viz, atrophy and linear pigmentation of the skin, localized alopecia, papilloma and marked syndactyly. FDH is an X-linked condition and any physician caring for children should consider this diagnosis of the illness of the patient (especially female) who presents with the above dermal and skeletal changes.