Kouji Narahara

Probable assignment of soluble isocitrate dehydrogenase (IDH1) to 2q33.3

SummaryGene 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.

Regional mapping of catalase and Wilms tumor--aniridia, genitourinary abnormalities, and mental retardation triad loci to the chromosome segment 11p1305----p1306.

SummaryGene 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.

Assignment of human porphobilinogen deaminase to 11q24.1→q24.2 by in situ hybridization and gene dosage studies

In situ hybridization and gene dosage-effect studies were conducted to determine the detailed chromosomal location of the gene encoding human porphobilinogen deaminase (PBGD). Red cell PBGD activity was normal in one patient with monosomy for 11q24.2----qter but was increased 1.5 times in another patient with trisomy for 11q22.2----qter. The cDNA probe for PBGD was found to be specifically hybridized to band 11q24. These results suggest that the gene for PBGD is localized within the region 11q24.1----q24.2.

Autosomal dominant congenital cataract and microphthalmia associated with a familial t(2;16) translocation

SummaryWe describe a family in which autosomal dominant congenital cataract and microphthalmia were segregating together with a reciprocal translocation t(2; 16) (p22.3;p13.3) through three generations. This family included four individuals with balanced translocations, three with partial trisomy 2p derived from this translocation, and two with a normal karyotype. All of the subjects with balanced and unbalanced translocations had congenital cataract and microphthalmia, whereas the two individuals with normal karyotypes did not show any ocular anomalies. These observations suggest that the altered function of a gene that lies on the 16p13.3 band and that has an important role in the development of the eye is responsible for this disorder.

Probable inverted tandem duplication of Xp in a 46,Xp+Y boy

SummaryA mentally retarded 16-month-old boy with subnormal stature, strabismus, anteverted nares and deformed ears was found to have a de novo structural rearrangement of the X chromosome (46,Xp+Y). The banding patterns of the abnormal X chromosome were interpreted to be an inverted tandem duplication of the segment Xp22.1→Xp22.3. Several other possibilities were considered but thought less likely. DNA replication studies with BrdU incorporation revealed the replication pattern of the duplicated segment to be similar to the equivalent portion of the X chromosome.

Assignment of ABO locus to 9q31.3----qter by study of a family in which an intrachromosomal shift involving chromosome 9 is segregating

SummaryA family in which an intrachromosomal shift, dir ins(9) (q22.1q31.3;q34.3), was segregating is described. A meiotic crossing over in the noninsertional loop of the carrier mother appeared to have resulted in the proband with a recombinant chromosome 9 duplicating the interstitial segment 9q22.1→q31.3. The study of ABO and AK1 phenotypes in the family showed that the proband was also a recombinant for the ABO locus. These results allowed us to assign the ABO locus to 9q31.3→qter on the cytogenetic basis.

Duplication of 2p25: confirmation of the assignment of soluble acid phosphatase (ACP1) locus to 2p25

SummaryThe regional localization of the gene coding for soluble acid phosphatase (ACP1) has been under debate in the two different chromosome regions, 2p23 or 2p25. Gene dosage studies in a case with a karyotype of 46,XX,dir dup(2) (p25.1→p25.3) showed that the ACP1 activity was increased to 1.4 times the mean value of normal individuals with the same ACP1 phenotype, while the level of soluble malate dehydrogenase (MDH1) was normal. These gene dosage effects indicated that the ACP1 gene locus can be mapped to 2p25.

A case of a reciprocal translocation between the Y and No. 1 chromosomes

SummaryA reciprocal translocation between the Y and No. 1 chromosomes was found in a male infant with psychomotor retardation and infantile spasms. The karyotype was designated as 46,X,t(1; Y) (q21; q11) on the basis of G- and Q-banding analyses. Previously reported cases with Y/autosomal translocations are reviewed.

Tissue-specific mosaicism for trisomy 21 and congenital heart disease

Cytogenetic studies in a girl with ventricular septal defect and mosaicism for trisomy 21 showed that trisomy was present in most cells from the myocardium and lung but in only a minority from the skin and lymphocytes. These findings emphasize the importance of tissue-specific mosaicism as a cause of certain cardiovascular diseases.

The critical monosomic segment involved in 4p- syndrome: A high-resolution banding study on five inherited cases

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) (p15.2;p11.21)mat (two cases, related). The results suggested that monosomy for the proximal half of the 4p16 band is sufficient to express 4p-syndrome.