Regional assignment of arylsulfatase A,mitochondrial aconitase and NADH-cytochrome b5 reductase by somatic cell hybridization

Summary By using somatic cell hybrids between HPRT deficient hamster cells and fibroblasts derived from a patient with a X/22 translocation t(X;22)(q13;q112), we have assigned the genes for human ARSA, DIA 1, and ACO 2 to region q112qter of human chromosome 22 and the gene for human PGK close to the breakpoint in band Xq13.     

Regional mapping of the gene for human UDPGal 4-epimerase on chromosome 1 in mouse-human hybrids

Somatic cell hybrids between mouse and human cells containing two different reciprocal translocations involving human chromosome 1, 46,X,t(1;X)(q12;q26) and 47,XX,+21,t(1;17)(p32;p13), were studied for the expression of human uridine diphosphate galactose 4-epimerase (UDPGal 4-epimerase, E.C. 5.1.3.2) by starch-gel electrophoresis. Analysis of the hybrid clones for the expression of the enzyme and the presence of the translocation chromosome 1 has permitted the assignment of the gene for human UDPGal 4-epimerase to the pter yields p32 region of chromosome 1.     

Regional localization of alpha-galactosidase (GLA) to Xpter----q22, hexosaminidase B (HEXB) to 5q13----qter, and arylsulfatase B (ARSB) to 5pter----q13

Two series of somatic cell hybrids were made by fusion of human cells with karyotypes 46,X,t(X;2;15)(q22;p12;p12) and 46,XX,t(5;7)(q13;p15) and rodent cells. Chromosome and isozyme analysis of human chromosomes and gene products in the hybrids localized GLA to Xpter----q22, HEXB to 5q13----qter, in both cases narrowing the regional assignments, and ARSB to 5pter----q13.     

Relationship of the human protooncogene CBL2 on 11q23 to the t(4;11), t(11;22), and t(11;14) breakpoints

A probe identifying CBL2, the human cellular homolog of the murine oncogene v-cbl and murine cellular protooncogene Cbl-2, and panels of rodent X human somatic cell hybrids were used to study the relationship of this protooncogene to translocations associated with acute leukemia, lymphoma, and Ewing sarcoma. CBL2 was mapped to 11q23 and found to translocate from chromosome 11 to 4 in an acute leukemia cell line possessing a t(4;11)(q21;q23) and from chromosome 11 to 14 in a B-cell lymphoma with a t(11;14)(q23;q32). In an Ewing sarcoma cell line with a t(11;22)(q23;q12), however, CBL2 remained on chromosome 11. Additional studies of other genes in the region of 11q23 allowed the following ordering of these genes and breakpoints: 11cen--q23--NCAM--CD3(E-D-G)--[t(11;14), t(4;11)]--(THY1, CBL2, ETS1)--t(11;22)--11qter. The gross structure of the CBL2 sequences examined was not altered by either of the flanking breakpoints. Given that the 5' and 3' ends of the CBL2 gene are not known and are probably not evaluated by the v-cbl probe, these results do not rule out the possibility of CBL2 involvement in the pathogenesis of a subset of acute leukemias possessing a t(4;11), B-cell lymphomas possessing a t(11;14), or Ewing sarcomas possessing a t(11;22).     

Disruption of DMD and deletion of ACSL4 causing developmental delay, hypotonia, and multiple congenital anomalies

We have studied a male patient with significant developmental delay, growth failure, hypotonia, girdle weakness, microcephaly, and multiple congenital anomalies including atrial (ASD) and ventricular (VSD) septal defects. Detailed cytogenetic and molecular analyses revealed three de novo X chromosome aberrations and a karyotype 46,Y,der(X)inv(X) (p11.4q11.2)inv(X)(q11.2q21.32 approximately q22.2)del(X)(q22.3q22.3) was determined. The three X chromosome aberrations in the patient include: a pericentric inversion (inv 1) that disrupted the Duchenne muscular dystrophy (DMD) gene, dystrophin, at Xp11.4; an Xq11.2q21.32 approximately q22.2 paracentric inversion (inv 2) putatively affecting no genes; and an interstitial deletion at Xq22.3 that results in functional nullisomy of several known genes, including a gene previously associated with X-linked nonsyndromic mental retardation, acyl-CoA synthetase long chain family member 4 (ACSL4). These findings suggest that the disruption of DMD and the absence of ACSL4 in the patient are responsible for neuromuscular disease and cognitive impairment.     

Cloning and mapping of members of the MYM family.

Tandem repeats of a novel, putative, zinc-binding motif (MYM) have been described within the products of two, highly homologous genes: ZNF198/RAMP/FIM and ZNF261/DXS6673E. ZNF198, mapping to 13q11-q12, was recently shown to fuse to the fibroblast growth factor receptor 1 gene in the t(8;13)(p11;q11-q12) rearrangement associated with a stem cell leukemia/lymphoma syndrome. ZNF261 at Xq13.1 is disrupted by a t(X;13)(q13.1;q32) rearrangement in a mentally retarded patient and is a candidate gene for nonspecific X-linked mental retardation. Here we have cloned another member of this family, designated ZNF258, and mapped it to chromosome band 14q12. In addition, ZNF262/KIAA0425 was identified as a further member of the family and mapped to 1p32-p34. The predicted protein products of ZNF258 and ZNF262 maintain the repeats of the MYM motif. Isolation of these new members will facilitate the functional characterization of the MYM family and motif.     

Ring chromosome 8 and translocation t(8;21) in a patient with acute myeloblastic leukemia

Recurrent translocation t(8;21)(q22;q22) acute myeloid leukemia (AML) is often associated with secondary chromosome changes of which the clinical significance is not clear since they do not seem to impair the prognosis. Uncommon chromosome changes may lead to the identification of leukemogenetic factors associated with t(8;21) since the AML1/RUNX1-ETO fusion gene resulting from the translocation is thought to be unable alone to induce leukemia. We here report a patient with AML, t(8;21) and ring chromosome 8 resulting in partial chromosome 8 deletion. Another patient with partial 8q deletion has been previously reported. It is suggested that more attention be paid to the genes located in distal 8q in relation to leukemogenesis.