Confirmation of regional assignment of nucleoside phosphorylase (NP) on chromosome 14 by gene dosage studies

Summary Gene dosage studies yielded results consistent with assignment of the locus for nucleoside phosphorylase to band 14q13. The red blood cells from a patient with the karyotype 47,XX,+der(14),t(8;14)(8qter8q24: :14q2114pter)pat had enzyme activity 50% higher than red cells from 47 normal controls, two trisomies involving chromosomes other than 14, and five balanced translocations involving chromosome 14. On the other hand, the red cells of a case with a karyotype 45,XX,-14,-22,+der(22),t(14;22)(14qter14q11 or 14q12::22p1122qter)mat and a case with a karyotype 47,XX, +der(14),t(14;16)(14pter14q11::16q2416qter)mat had normal activity.     

A deletion panel of the long arm of the X chromosome: subregional localization of 22 DNA probes

Summary Two males and two females with different but overlapping deletions on the proximal long arm of the X chromosomes have been investigated. Their karyotypes, which have been well characterized by high resolution banding techniques, are 46,Y,del(X)(pterq21.1:: q21.33qter); 46,Y,del(X) (pterq21.2::q21.31qter); 46,X,del(X) (pterq21.31::q24.3qter) and 46,X,del (X)(pterq21.1:). A deletion panel, which makes it possible to subdivide the long arm of the X chromosome into seven subregions, has been established using the genomic DNA from the four families, and applied to the fine subregional localization of the loci for 22 DNA probes. Based on the results obtained, the possible location of the loci in question has been narrowed down considerably, in some cases to an area of only 5% of the previously assigned region; hybridization to Southern blots of a panel with well-characterized chromosome deletions is thus a powerful means of localizing DNA probes, especially with respect to the X probes.Part of the results from this investigation were published at Human Gene Mapping 9 as abstracts     

Production of a novel syrup containing neofructo-oligosaccharides by the cells of Penicillium citrinum

A novel syrup containing neofructo-oligosaccharides was produced from sucrose (Brix 70) by whole cells of Penicillium citrinum. The efficiency of fructo-oligosaccharides production was more than 55% and those of the main carbohydrate components, 1-kestose (Fruf 21Fruf 21 Glc), nystose (Fruf 21Fruf 21 Fruf 21 Glc) and neokestose (Fruf 26 Glc12 Fruf), were 22, 14 and 11%, respectively.     

Regional mapping of the locus for hexokinase-1 (HK1) to 10p11→q23 by gene dosage in human fibroblasts

Summary The hexokinase (HK) activity in human fibroblasts was close to that expected for a gene dosage effect in a mosaic cell line with about 86% trisomy 10 cells (64% greater than four control lines with normal karyotypes). There was no dosage effect for HK in the cell line that was trisomic for 10q24qter, nor in the cell line monosomic for 10pterp12. The data suggest an assignment of the HK1 locus (the only hexokinase in fibroblasts) to 10p11q23 by exclusion.     

A new translocation t(1;4;11) in congenital acute nonlymphocytic leukemia (acute myeloblastic leukemia)

Summary A new translocation t(1;11;4)(1pter1p32::11q23 11q13::4p164qter) was found in the peripheral blood of a patient with congenital acute myeloblastic leukemia (AML). It was concluted that this translocation may represent a new mutation, which caused the leukemia with very high leukocytosis, hepatosplenomegaly, leukemic infiltration of the majority of the organs, and a very poor prognosis.     

Adjacent 2 meiotic disjunction. Report of a case resulting from a familial 13q;15q balanced reciprocal translocation and review of the literature

Summary An abnormal short-lived female infant with almost complete trisomy 13 (pterq32 or 33) and partial monosomy 15 (pterq14 or 15) resulting from an adjacent 2 meiotic disjunction of a paternal reciprocal translocation is described. Cases with monosomy of chromosome 15 material are reviewed. It appears likely that monosomy of an interstitial long arm segment, approximating to 15q2124, imparts the lethality associated with the full monosomic condition. Adjacent 2 disjunction in man has been further characterised by reviewing the literature.     

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

Summary 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)(pterp13::p11.11qter) for case 1 and 46,XY,t(2;17) (q23;q25), del(11) (pterp13::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 (11p1305p1306). 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 11p1305p1306, 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.     

X long-arm deletions. A review of non-mosaic cases studied with banding techniques

Summary A woman with secondary amenorrhoea and an X long-arm deletion (pterq21:) is described and compared with 30 adult non-mosaic, banded cases. Approximately 50% of the patients had gonadal dysgenesis associated with a higher frequency of short stature and Turner stigmata than in women with indication of ovarian activity. It is suggested that preservation of bands Xq2628 may be decisive for normal ovarian function.Supported by grants to E.N. from the P. Carl Petersen's Foundation (B995) and the Danish Medical Research Council (512-4276).     

Unbalanced translocation between chromosomes 2 and 7 with de novo deletion of band 35 on the long arm of chromosme 2

Summary Clinical and cytogenetical findings are described in an infant with a de novo deletion of the long arm of chromosome 2. The boy's karyotype is 46,XY, rec(2)delq,t(2;7) (2pter2q34::7p217pter) (7qter7p21::2q362qter). He showed developmental retardation, low-set ears, micrognathia, short neck, abundant skin of the neck, tetralogy of Fallot, bipartite labialike scrotum, clitorislike penis, cryptorchism, and deformities of the hands and feet.     

Tertiary trisomy (22q11q),47,+der(22),t(11;22)

Summary We describe a case of tertiary trisomy (22q11q) 47,XX,+der(22),(22pter22q13: : 11q2511qter) in a child with mental retardation, cleft palate, and congenital heart disease resulting from 3: 1 meiotic nondisjunction in a maternal (11;22) translocation carrier. The clinical findings in previously reported cases are reviewed and compared with the features of reported patients with partial trisomy 11q and trisomy 22 syndromes. Half of the ten reported families had additional balanced translocation carriers who may have an increased risk of having a liveborn child with an MCA/MR syndrome, although none have been reported to date.     

Possible intrachromosomal duplication in a case of trisomy 9p

Summary A 5-year-old boy with multiple minor anomalies and mental retardation was found to have chromosomal condition of 46,XY,inv dup(9p)(pterp13::p21p24::p13qter). The clinical features of the propositus fit well with those of trisomy 9p which have been established to be a clinical entity.     

Partial trisomy of 11 and 22 due to familial translocation t(11;22) (q23;q11), inherited in three generations

Summary A 1-year-old girl with partial trisomy of 11 (q23qter) and 22 (pterq11) is presented. She had severe mental retardation, cleft palate, congenital heart disease, congenital dislocation of the hip, and other anomalies.The extra acrocentric chromosome was identified as der(22),t(11;22) (q23;q11) from a familial translocation and by G-and R-banding methods. The mother and the maternal grandfather were carriers of balanced rcp(11;22) (q23;q11) translocations.The possible relations between phenotypic features and the karyotypes of partial trisomy 11 and 22 are discussed.     

Transposition of 9q34 and 22 (q11→qter) regions has a specific role in chronic myelocytic leukemia

Summary Six cases are reported of variant Ph translocations found among 240 patients with Ph-positive CML. Five cases had a three-chromosome rearrangement involving, in addition to chromosomes 9 and 22, chromosomes 7, 4, 2(two), and 3 respectively, and one case had a two-chromosome rearrangement 22/5. A review of the literature revealed that three- and two-chromosome variant Ph translocations are observed with equal frequency. It is postulated that all variant translocations are indeed three-chromosome rearrangements, that the specific event for the formation of the Ph chromosome is the reciprocal translocation 9/22, and that the transposition of regions 9q34 and 22 (q11qter), plays a major role in the development of CML.     

Translocation t(7p+; 13q-) associated with recurrent abortion

Summary A balanced translocation was found in a normal female with a history of four abortions. On the basis of the Giemsa-banding pattern the abnormality was interpreted as to be a translocation of a part of the long arm of chromosome 13 to the short arm of chromosome 7:t(7;13)(7qter7p22::13q1413qter;13q1413pter::7p227pter). Problems in genetic counseling are discussed with respect to this case.Supported by the Forschungsprojekt Medizinische und soziale Probleme der menschlichen Reproduktion des Ministeriums für Gesundheitswesen der DDR.     

Possible complex translocation t(9; 14; 13)(q12;pl?;q31) in mother of a child with 9p-trisomy syndrome

Summary A mentally retarded boy with trisomy 9p is described. This trisomy arose through aberrant segregation of translocation chromosome during meiosis in his mother, who has a complex translocation involving chromosomes 9, 13, and 14. Based on both G-, Q-banding, and DNA replication patterns, the patient's karyotype was identified as 47,XY,-13, +(9;13) (9pter9q12::13q3113qter), +t(13;14) (13pter13q31::14pl?14pter). We suppose his mother's karyotype to be 46,XX,-9,-13,-14,+t(9;13) (9pterq12::13q3113qter), +t(13;14) (13pter13q31::14pl?14pter), +t(9;14) (9qter9q12::14pl?14qter). His phenotypically normal brother and sister are also carriers, having the same translocation chromosome as their mother. Clinical findings of the patient included peculiar face with hypertelorism, prominent nasal bridge and deformed helix, marked delay of osseous development, hypoplastic phalangia in fingers and toes, dysplastic nails and absence of digital triradii.     

SOD-A and chromosome 21

Summary A balanced maternal chromosome translocation (9p24;21q214) resulted in two offspring with unbalanced karyotypes. One of these, a girl trisomic for both segment 9pter9p24 and segment 21pter21q214, was found to have a SOD-A activity not significantly different from those found in a group of five cases with trisomy 21. However, clinical evaluation of this girl revealed no symptoms of the Down syndrome. These findings suggest that, providing the gene dosage theory is correct, the gene for SOD-A is probably localized on chromosome 21 proximal to, or in, band q21.     

10q(q23→qter) duplication: GOTs,HK1, and other gene markers

Summary Gene marker analyses have been carried out in a patient with 10q(q23qter) duplication. The observed elevation of red cell glutamic oxaloacetic transaminase activity is compatible with earlier somatic cell hybridization studies that mapped the locus to this region. Hexokinase-1 activity in the red cells was normal, which is consistent with its prior assignment to the unaffected part of chromosome 10 (10pterq23).     

A missense mutation (G197→A) in theα-l-fucosidase gene of fucosidosis patients leads to loss ofα-l-fucosidase

Fucosidosis is an autosomal recessive lysosomal storage disease resulting from the absence of -l-fucosidase activity. Two natural missense mutations (G¹⁹⁷A) and (A⁸⁶⁰G) within the -l-fucosidase gene have been reported to be homozygous in four patients with fucosidosis. Expression of wild-type and mutated -l-fucosidase cDNAs in COS-1 cells revealed complete deficiency of -l-fucosidase for the G¹⁹⁷A transition and a normal level of enzyme for A⁸⁶⁰G. We therefore conclude that the change of G¹⁹⁷A is responsible for fucosidosis in the patients while A⁸⁶⁰G is a normal polymorphic variant of -l-fucosidase.     

Association of a new chromosomal deletion [del(1)(q32q42)] with diaphragmatic hernia: assignment of a human ferritin gene

Summary A newborn male with a large diaphragmatic hernia presented in severe respiratory distress. Additional features included a paucity of subcutaneous tissue, mild facial dysmorphism, webbing of the neck, genital hypoplasia, and flexion contractures of the fingers. His karyotype showed a previously unreported de novo interstitial deletion of the long arm of chromosome 1[46,XY,de(1)(pterq32.3::q42.3qter)]. Regional mapping of five human genes that have been provisionally assigned to chromosome 1 was performed by restriction analysis of genomic DNA from this patient. Glucocerebrosidase, H4 histone, renin, and alpha-spectrin genes mapped outside the delected region, whereas an H subunit of the ferritin gene mapped to 1q32q42. These results indicate the utility of chromosomal deletions in gene mapping, and the importance of karyotype analysis in newborns with diaphragmatic hernias.     

Structural analyses of new tri- and tetrasaccharides produced from disaccharides by transglycosylation of purified Trichoderma viride β-glucosidase

A new -glucosidase was partially purified from Trichoderma viride cellulase. This -glucosidase catalyzed a transglycosylation reaction of cellobiose to give -D-Glc-(16)--D-Glc-(14)-D-Glc (1, yield: 18.8%) and -D-Glc-(16)--D-Glc-(16)--D-Glc-(14)-D-Glc (2, 3.7%), regioselectively. Furthermore, the enzyme regioselectively converted laminaribiose and gentiobiose into -D-Glc-(16)--D-Glc-(13)-D-Glc (3, 15.3%) and -D-Glc-(16)--D-Glc-(16)-D-Glc (4, 20.2%), respectively. The structures (1–4) of the products were determined by ¹H and ¹³C NMR spectroscopies. This high regio- and stereoselectively of the -glucosidase could be applied for oligosaccharide synthesis.