Translocation 46,XY,t(2;5) (q37;q14) and mental retardation. Clinical and cytogenetic study]

A boy, suffering from severe mental and motor retardation, was found to be the carrier of an apparently balanced chromosomal rearrangement studied by autoradiography and fluorescence.     

Mapping of the versican proteoglycan gene (CSPG2) to the long arm of human chromosome 5 (5q12-5q14).

Versican is a major chondroitin sulfate proteoglycan of vascularized connective tissues whose eponym reflects its functional versatility in macromolecular affinity and interactions. In this report we have localized the versican gene (CSPG2) to the long arm of human chromosome 5 by utilizing a combination of somatic cell hybrids, Southern blotting, polymerase chain reaction, and chromosomal in situ hybridization. The proteoglycan gene segregated concordantly with hybrid cell lines containing the long arm of chromosome 5, comprising the 5q12-q14 band regions. To refine this locus further, we screened a chromosome 5-specific library and isolated several genomic clones encoding a portion of the 5' end of versican. One of these genomic clones was used as a probe for in situ hybridization of human chromosome metaphases. The results corroborated the data obtained using somatic cell hybrids and further refined the assignment of the versican gene to the narrow band region of 5q12-5q14, with the primary site likely to be 5q13.2. The availability of novel genomic clones and the mapping data presented here will make possible the identification of any defect genetically linked to this proteoglycan gene.     

Some clinical and cytogenetic observations on a ring chromosome 13 (p11 q34).

A girl of 9-10/12 years of age with 46,XX,r(13)(p11q34) karyotypes was studied. She presented some clinical and radiological features, such as pectus excavatum, scalp alopecic area, 12th rib agenesis, hypoplastic pelvis, small gluteal pits and hypoplasia of the external genitalia in a female, which have never been previously described in other cases with ring 13 chromosomes. Cytogenetically, in vivo and in vitro viability of complete monosomic and partially trisomic and tetrasomic cells was found. The presence of nucleolus organizer regions and association of the ring 13 with other acrocentrics question the exclusivity of these attributes to acrocentrics p12.     

Clinical, cytogenetic, and molecular characterization of seven patients with deletions of chromosome 22q13.3.

We have studied seven patients who have chromosome 22q13.3 deletions as revealed by high-resolution cytogenetic analysis. Clinical evaluation of the patients revealed a common phenotype that includes generalized developmental delay, normal or accelerated growth, hypotonia, severe delays in expressive speech, and mild facial dysmorphic features. Dosage analysis using a series of genetically mapped probes showed that the proximal breakpoints of the deletions varied over approximately 13.8 cM, between loci D22S92 and D22S94. The most distally mapped locus, arylsulfatase A (ARSA), was deleted in all seven patients. Therefore, the smallest region of overlap (critical region) extends between locus D22S94 and a region distal to ARSA, a distance of > 25.5 cM.     

The chromosome breakpoint at 14q32 in an ataxia telangiectasia t(14;14) T cell clone is different from the 14q32 breakpoint in Burkitts and an inv(14) T cell lymphoma

Summary The T cell receptor chain gene locus and the immunoglobulin heavy chain gene locus (IgH) have previously been mapped to the q11 and q32 positions respectively of the human chromosome 14. Both of these sites are also common breakpoints in lymphocytes from ataxia telangiectasia (A-T) patients. Using in situ hybridisation we show that the 14q32 breakpoint in an A-t non-leukaemic T cell clone with t(14;14) translocation, lies outside the IgH locus and proximal to it with respect to the centromere. The 14q11-14qter segment of the homologous chromosome 14 carrying the constant gene region of the chain locus is translocated to this 14q32 position.     

Partial duplication 5q syndrome: phenotypic similarity in two sisters with identical karyotype (partial duplication 5q33 leads to 5qter and partial deficiency 8p23 leads to pter).

Two sisters with statomotor developmental retardation microcephaly, hydrocephalus internus and externus without signs of pressure, heart defect (ventricular septal defect), early pulmonary resistance and characteristic facial changes were found to have the same unbalanced karyotype with partial trisomy 5q3300 leads to 5qter and partial monosomy 8p2300 leads to 8pter, derived from a balanced reciprocal paternal translocation: 46,XY,t(5;8)(q3300;p2300). The older girl was tested for the erythrocyte enzyme glutathion reductase. She had normal values.     

Inherited pericentric inversion of chromosome no. 2 with Robertsonian translocation (13q 14q) resulting in trisomy for chromosome 13q

This report includes a patient with an inherited pericentric inversion of chromosome No. 2 in addition to a Robertsonian translocation resulting in trisomy for chromosome 13q. The chromosomal constitution of the proband was 46,XX,inv(2) (pter leads to p11 : : q14 leads to p11 : : q14 leads to qter); t(13,14) (13qter leads to 13p11 : : 14q11 leads to 14qter). Sequential QFQ, RFA and GTG banding techniques were employed on the chromosomes of all family members. The chromosomal constitutions of the father and his first child were normal while the mother had an inversion of chromosome No. 2 [46,XX,inv(2) (pter leads to p11 : : q14 leads to p11 : : q14 leads to qter)]. The proband inherited this abnormal chromosome. In addition, she had a de novo Robertsonian translocation involving chromosomes 13q and 14q resulting in trisomy of chromosome 13q.     

New data on clonal anomalies of chromosome 14 in ataxia telangiectasia: tct (14;14) and inv(14)

Summary From a series of 53 patients with ataxia telangiectasia, two large clones with a t tan or tct(14;14) and two with an inv(14) were observed among phytohaemagglutinin (PHA)-stimulated lymphocytes. Smaller clones with the same inv(14) were observed in two other cases. Similar breakpoints may exist, both for t(14;14) and inv(14): q11.1/q11.2 and q32, and it is postulated that the rearrangements are related to a recombination of the -chain of the T-cell receptor and IgH clusters of genes.     

Assignment of FUT8 to chicken chromosome band 5q1.4 and to human chromosome 14q23.2-->q24.1 by in situ hybridization. Conserved and compared synteny between human and chicken

The human FUT8 gene is implicated in crucial developmental stages and is overexpressed in some tumors and other malignant diseases. Based on three different experiments we have assigned the FUT8 gene to chromosome bands 14q23.2-->q24.1 and not 14q24.3 as previously shown (Yamaguchi et al., 1999). We found a high degree of identity between human and chicken FUT8 sequences. We mapped the chicken FUT8 gene to chromosome 5q1.4 in an internal rearrangement of a region of conserved synteny described between human 14q and chicken chromosome 5. Based on these findings we propose a new gene position correspondence between chicken and human comparative maps.     

Assignment of a serotonin 5HT-2 receptor gene (HTR2) to human chromosome 13q14-q21 and mouse chromosome 14

A gene for serotonin 5HT-2 receptor (HTR2) is assigned to human chromosome 13 by somatic cell hybrids and to region 13q14-q21 by in situ hybridization. It is assigned to mouse chromosome 14 by somatic cell hybrid analysis.     

Molecular cytogenetic characterization of 17 rob(13q14q) Robertsonian translocations by FISH, narrowing the region containing the breakpoints.

We have characterized 17 rob(13q14q) Robertsonian translocations, using six molecular probes that hybridize to the repetitive sequences of the centromeric and shortarm regions of the five acrocentric chromosomes by FISH. The rearrangements include six de novo rearrangements and the chromosomally normal parents, five maternally and three paternally inherited translocations, and three translocations of unknown origin. The D21Z1/D13Z1 and D14Z1/D22Z1 centromeric alpha-satellite DNA probes showed all rob(13q14q) chromosomes to be dicentric. The rDNA probes did not show hybridization on any of the 17 cases studied. The pTRS-47 satellite III DNA probe specific for chromosomes 14 and 22 was retained around the breakpoints in all cases. However, the pTRS-63 satellite III DNA probe specific for chromosome 14 did not show any signals on the translocation chromosomes examined. In 16 of 17 translocations studied, strong hybridization signals on the translocations were detected with the pTRI-6 satellite I DNA probe specific for chromosome 13. All parents of the six de novo rob(13q14q), including one whose pTRI-6 sequence was lost, showed strong positive hybridization signals on each pair of chromosomes 14 and 13, with pTRS-47, pTRS-63, and pTRI-6. Therefore, the translocation breakpoints in the majority of rob(13q14q) are between the pTRS-47 and pTRS-63 sequences in the p11 region of chromosome 14 and between the pTRI-6 and rDNA sequences within the p11 region of chromosome 13.     

An unusually large 5q duplication in an adult female subject: spreading of inactivation and in vitro instability of the derivative Xp/5q chromosome

An unbalanced translocation resulting in an unusually large partial 5q trisomy (5q11-5qter) and partial Xp monosomy (Xp11-Xpter) is reported in a 24 yr old woman with phenotypic abnormalities including gonadal dysgenesis and mental retardation. The karyotypes of the parents and the brother were found normal. Peripheral blood stimulated lymphocytes and cutaneous fibroblasts of the proband exhibited constantly, after BrdU incorporation, selective inactivation of the derivative X;5 chromosome spreading to the 5q duplicate segment. A variety of numerical and structural changes involving the derivative chromosome were observed in about 10% of cells of the cultured lymphoblastoid line established from the subject's lymphocytes. The extended 5q duplication, according to the literature, is generally accompanied by a severe phenotype and by developmental failure; it is therefore believe that genetic inactivation of the 5q duplicated region permitted the proband's development to adult age, despite the profound chromosomal imbalance.     

Inverted duplication of JH associated with chromosome 14 translocation and T-cell leukemia in ataxia-telangiectasia.

A specific 14q32 breakpoint is observed in a homologous chromosome 14 translocation [t(14;14)q12q32] occurring in the T-cells of about 10% of patients with ataxia-telangiectasia (AT). To investigate whether the 14q32 breakpoint in AT occurs within the immunoglobulin gene cluster as is frequently detected in B-cell lymphoma, immunoglobulin clones were hybridized to Southern blots of DNA isolated from the T-cells of two AT patients with this chromosome 14 translocation. The 14q32 translocation breakpoints in these patients are apparently not within JH, S mu, C mu, S alpha-1 or -2, or C alpha-1 or -2, but one of the patients has an inverted duplication of at least 26 kilobases (kb) of the C mu region, with an associated 5' flanking deletion. The point of origin of the inverted duplication is within JH near the recombination signal for the J4 gene. This suggests that normal JH recombination mechanisms may have played a role in the development of this 14q32 chromosomal aberration. The presence of AT chromosomal breakpoints near other rearranging genes suggests a role for exaggerated recombination in the pathogenesis of chromosomal instability in AT.