Gene dosage effects for soluble isocitrate dehydrogenase (IDH1) were investigated in four unrelated cases with abnormalities involving the long arm of chromosome 2. Case 1 was trisomic for 2q33.3----qter, Case 2 monosomic for 2q33.3----q35, Case 3 trisomic for 2q11.2----q24.2, and Case 4 monosomic for 2q23----q24.2. These abnormalities were de novo except in Case 1, where trisomy 2q resulted from a maternal translocation. The red cell IDH1 levels were significantly reduced in Cases 1 (41.4% of normal value) and 2 (51.9%), while they were normal in Cases 3 and 4. The low IDH1 level also in the father of Case 1 (43.6%), together with the common electrophoretic phenotype of IDH1 in red cells as well as leukocytes, led us to suppose that Case 1 was really heterozygous for common and probable null alleles, and that the IDH1 gene locus could be excluded from 2q33.3----qter. On the other hand, normal IDH1 values in the parents of Case 2 were consistent with the hemizygosity for this locus in Case 2. The results suggested that the IDH1 locus could be assigned to the 2q33.3 band, especially the proximal portion of it.

Gene-dosage and in situ hybridization study of plasminogen (PLG) and alpha-L-fucosidase 2 (FUCA2) was performed on two patients with a small deletion of the distal long arm of chromosome 6, to define the structural abnormality more precisely. The results led to the cytogenetic diagnosis of an interstitial 6q deletion, del(6)(q25.1q25.3), in one patient and of a terminal 6q deletion resulting from a paternal t(1;6)(q44;q2605) translocation in the other patient. The latter patient had congenital noncommunicating hydrocephalus due to obstruction at the level of the foramen of Monro or the third ventricle which has not previously been described in terminal 6q deletions. Review of the literature suggests the emergence of a clinical syndrome associated with terminal 6q deletions.

SummaryIn an attempt to determine the critical monosomic segment involved in 4p-syndrome, we studied the precise breakpoints of five inherited cases with the syndrome using a high-resolution banding technique. The 5 patients ranged in age at diagnosis from newborn to 15 months, 4 of whom could be clinically diagnosed as having 4p-syndrome. Common clinical features included mental retardation, low birth weight, growth failure, hypotonia, microcephaly, peculiar facial dysmorphia and ear malformations. Karyotypes of the 5 were 46,XX,-4, +der(4),t(4;21) (p16.1 ;q22.3)pat; 46,XX,-4,+der(4), inv ins(4;9)(p15.32p16.3;q34.3)pat; 46,XX, rec(4),del p,inv(4)(p15.2q35)pat; and 46,XX,-4, + der(4),t(4;18) (pl5.2;pll.21)mat (two cases, related). The results suggested that monosomy for the proximal half of the 4p16 band is sufficient to express 4p-syndrome.

Gene dosage effects for catalase (CAT) were studied in two unrelated patients with an interstitial deletion involving 11p13 to determine precisely the sites of the genes for CAT and the Wilms tumor--aniridia, genitourinary abnormalities, and mental retardation triad (WAGR) in the 11p13 band. Case 1 had the aniridia-Wilms tumor association, and case 2 showed the AGR triad. The karyotypes identified by high resolution banding techniques were 46,XY,del(11)(pter----p13::p11.11----qter) for case 1 and 46,XY,t(2;17)(q23;q25),del(11)(pter----p13::p11.2----qter) for case 2. In both cases, the distal breakpoints of the deleted chromosomes 11 appeared to have occurred on the middle portion of 11p13 (11p1305----p1306). The level of erythrocyte CAT activities in case 1 was reduced (47% of normal), while that in case 2 was normal. The results suggested not only that both the CAT and WAGR should be mapped to chromosome region 11p1305----p1306, but also that in this region the CAT locus is more distally placed than the WAGR locus. Because of the proximity of the two gene loci, assays of erythrocyte CAT may be useful to identify a submicroscopic deletion in some patients with sporadic aniridia and to predict a risk of developing Wilms tumor.

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